Pharmacological analysis of the activity of the adenosine uptake inhibitor, dipyridamole, on the sinoatrial and atrioventricular nodes of the guinea‐pig
Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N‐ethylcarboxamidoadenosine (NECA) concentration‐effect (E/[A]) curves were compared on the AV node, in guinea‐pig isolated perfused hearts, and on the SA...
Saved in:
Published in | British journal of pharmacology Vol. 124; no. 4; pp. 729 - 741 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.06.1998
Nature Publishing |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N‐ethylcarboxamidoadenosine (NECA) concentration‐effect (E/[A]) curves were compared on the AV node, in guinea‐pig isolated perfused hearts, and on the SA node, in isolated right atria, by measuring dromotropic and chronotropic responses, respectively. In the absence of dipyridamole, adenosine was significantly more potent on the AV node than SA node (AV p[A]50=4.95±0.10, SA p[A]50=3.62±0.10). In contrast, NECA and adenosine in the presence of dipyridamole were approximately equiactive in the two assays (NECA: AV p[A]50=7.07±0.07; SA p[A]50=7.30±0.08; adenosine: AV p[A]50=6.49±0.08; SA p[A]50=6.27±0.05). Dipyridamole was significantly more potent in enhancing the effects of adenosine on the SA node than on the AV node (pKi values estimated by Kenakin's method (1981): AV node=8.18±0.14; SA node=8.75±0.08).
The difference in pKi values did not appear to be due to dipyridamole expressing other actions because concentrations of dipyridamole which saturated the adenosine transporter had no effect on the NECA E/[A] curves in either assay. However, the test of another assumption of Kenakin's method, that adenosine taken up into cells is pharmacologically inactive, failed on the AV node assay because a significant potentiating interaction was found between adenosine and NECA. The interaction was concentration‐dependent, reciprocal to the extent that pre‐incubation with either agonist potentiated the other and was concluded to be due to an intracellular action of adenosine as the potentiation disappeared in the presence of dipyridamole.
An explanatory model was developed to account for the data obtained using existing pharmacological concepts of ligand action in isolated tissue bioassays. In the model, adenosine, but not NECA, was assumed to be subject to saturable agonist uptake, an uptake which was competitively blocked by dipyridamole. Adenosine and NECA were assumed to act extracellularly at adenosine A1‐receptors. In the AV node, but not the SA node, the adenosine transported into the cells was assumed to potentiate the effects of adenosine A1‐receptor activation. For the AV node assay, the model predicted that potentiation of adenosine by uptake blockade is offset by a simultaneous decrease in potentiation due to the intracellular action of adenosine. All of the experimental data obtained in the study could be accounted for by the model including the apparent differences in potency of adenosine in the absence of dipyridamole and the pKi values for dipyridamole. |
---|---|
AbstractList | 1. Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N-ethylcarboxamidoadenosine (NECA) concentration-effect (E/[A]) curves were compared on the AV node, in guinea-pig isolated perfused hearts, and on the SA node, in isolated right atria, by measuring dromotropic and chronotropic responses, respectively. In the absence of dipyridamole, adenosine was significantly more potent on the AV node than SA node (AV p[A]5, = 4.95+/-0.10. SA p[A]50=3.62+/-0.10). In contrast, NECA and adenosine in the presence of dipyridamole were approximately equiactive in the two assays (NECA: AV p[A]50=7.07+/-0.07; SA p[A]50=7.30+/-0.08: adenosine: AV p[A]50=6.49+/-0.08; SA p[A]50=6.27+/-0.05). Dipyridamole was significantly more potent in enhancing the effects of adenosine on the SA node than on the AV node (pKi values estimated by Kenakin's method (1981): AV node 8.18+/-0.14; SA node=8.75+/-0.08). 2. The difference in pKi values did not appear to be due to dipyridamole expressing other actions because concentrations of dipyridamole which saturated the adenosine transporter had no effect on the NECA E/[A] curves in either assay. However, the test of another assumption of Kenakin's method, that adenosine taken up into cells is pharmacologically inactive, failed on the AV node assay because a significant potentiating interaction was found between adenosine and NECA. The interaction was concentration-dependent, reciprocal to the extent that pre-incubation with either agonist potentiated the other and was concluded to be due to an intracellular action of adenosine as the potentiation disappeared in the presence of dipyridamole. 3. An explanatory model was developed to account for the data obtained using existing pharmacological concepts of ligand action in isolated tissue bioassays. In the model, adenosine, but not NECA, was assumed to be subject to saturable agonist uptake, an uptake which was competitively blocked by dipyridamole. Adenosine and NECA were assumed to act extracellularly at adenosine A1-receptors. In the AV node, but not the SA node, the adenosine transported into the cells was assumed to potentiate the effects of adenosine A1-receptor activation. For the AV node assay, the model predicted that potentiation of adenosine by uptake blockade is offset by a simultaneous decrease in potentiation due to the intracellular action of adenosine. All of the experimental data obtained in the study could be accounted for by the model including the apparent differences in potency of adenosine in the absence of dipyridamole and the pKi values for dipyridamole. Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N‐ethylcarboxamidoadenosine (NECA) concentration‐effect (E/[A]) curves were compared on the AV node, in guinea‐pig isolated perfused hearts, and on the SA node, in isolated right atria, by measuring dromotropic and chronotropic responses, respectively. In the absence of dipyridamole, adenosine was significantly more potent on the AV node than SA node (AV p[A] 50 =4.95±0.10, SA p[A] 50 =3.62±0.10). In contrast, NECA and adenosine in the presence of dipyridamole were approximately equiactive in the two assays (NECA: AV p[A] 50 =7.07±0.07; SA p[A] 50 =7.30±0.08; adenosine: AV p[A] 50 =6.49±0.08; SA p[A] 50 =6.27±0.05). Dipyridamole was significantly more potent in enhancing the effects of adenosine on the SA node than on the AV node (pK i values estimated by Kenakin's method (1981): AV node=8.18±0.14; SA node=8.75±0.08). The difference in pK i values did not appear to be due to dipyridamole expressing other actions because concentrations of dipyridamole which saturated the adenosine transporter had no effect on the NECA E/[A] curves in either assay. However, the test of another assumption of Kenakin's method, that adenosine taken up into cells is pharmacologically inactive, failed on the AV node assay because a significant potentiating interaction was found between adenosine and NECA. The interaction was concentration‐dependent, reciprocal to the extent that pre‐incubation with either agonist potentiated the other and was concluded to be due to an intracellular action of adenosine as the potentiation disappeared in the presence of dipyridamole. An explanatory model was developed to account for the data obtained using existing pharmacological concepts of ligand action in isolated tissue bioassays. In the model, adenosine, but not NECA, was assumed to be subject to saturable agonist uptake, an uptake which was competitively blocked by dipyridamole. Adenosine and NECA were assumed to act extracellularly at adenosine A 1 ‐receptors. In the AV node, but not the SA node, the adenosine transported into the cells was assumed to potentiate the effects of adenosine A 1 ‐receptor activation. For the AV node assay, the model predicted that potentiation of adenosine by uptake blockade is offset by a simultaneous decrease in potentiation due to the intracellular action of adenosine. All of the experimental data obtained in the study could be accounted for by the model including the apparent differences in potency of adenosine in the absence of dipyridamole and the pK i values for dipyridamole. Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N‐ethylcarboxamidoadenosine (NECA) concentration‐effect (E/[A]) curves were compared on the AV node, in guinea‐pig isolated perfused hearts, and on the SA node, in isolated right atria, by measuring dromotropic and chronotropic responses, respectively. In the absence of dipyridamole, adenosine was significantly more potent on the AV node than SA node (AV p[A]50=4.95±0.10, SA p[A]50=3.62±0.10). In contrast, NECA and adenosine in the presence of dipyridamole were approximately equiactive in the two assays (NECA: AV p[A]50=7.07±0.07; SA p[A]50=7.30±0.08; adenosine: AV p[A]50=6.49±0.08; SA p[A]50=6.27±0.05). Dipyridamole was significantly more potent in enhancing the effects of adenosine on the SA node than on the AV node (pKi values estimated by Kenakin's method (1981): AV node=8.18±0.14; SA node=8.75±0.08). The difference in pKi values did not appear to be due to dipyridamole expressing other actions because concentrations of dipyridamole which saturated the adenosine transporter had no effect on the NECA E/[A] curves in either assay. However, the test of another assumption of Kenakin's method, that adenosine taken up into cells is pharmacologically inactive, failed on the AV node assay because a significant potentiating interaction was found between adenosine and NECA. The interaction was concentration‐dependent, reciprocal to the extent that pre‐incubation with either agonist potentiated the other and was concluded to be due to an intracellular action of adenosine as the potentiation disappeared in the presence of dipyridamole. An explanatory model was developed to account for the data obtained using existing pharmacological concepts of ligand action in isolated tissue bioassays. In the model, adenosine, but not NECA, was assumed to be subject to saturable agonist uptake, an uptake which was competitively blocked by dipyridamole. Adenosine and NECA were assumed to act extracellularly at adenosine A1‐receptors. In the AV node, but not the SA node, the adenosine transported into the cells was assumed to potentiate the effects of adenosine A1‐receptor activation. For the AV node assay, the model predicted that potentiation of adenosine by uptake blockade is offset by a simultaneous decrease in potentiation due to the intracellular action of adenosine. All of the experimental data obtained in the study could be accounted for by the model including the apparent differences in potency of adenosine in the absence of dipyridamole and the pKi values for dipyridamole. |
Author | Meijler, F L Shankley, N P Welsh, N J Black, J W Meester, B J |
AuthorAffiliation | Analytical Pharmacology, Rayne Institute, King's College School of Medicine & Dentistry, 123, Coldharbour Lane, London SE5 9NU, U.K 1 Interuniversity Cardiology Institute of the Netherlands, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands |
AuthorAffiliation_xml | – name: Analytical Pharmacology, Rayne Institute, King's College School of Medicine & Dentistry, 123, Coldharbour Lane, London SE5 9NU, U.K – name: 1 Interuniversity Cardiology Institute of the Netherlands, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands |
Author_xml | – sequence: 1 givenname: B J surname: Meester fullname: Meester, B J – sequence: 2 givenname: N P surname: Shankley fullname: Shankley, N P – sequence: 3 givenname: N J surname: Welsh fullname: Welsh, N J – sequence: 4 givenname: F L surname: Meijler fullname: Meijler, F L – sequence: 5 givenname: J W surname: Black fullname: Black, J W |
BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2334895$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/9690865$$D View this record in MEDLINE/PubMed |
BookMark | eNqFkc1uEzEUhS1UVNLClh2SFyw7wY7HP7NBohVQpEp0AWvrxvYkDhN7ZE-CZscjsO7j9UlwmmgEK1bX9vnuOZbOBToLMTiEXlMyp4Spd3kzX276OZGEqmbxDM1oLUXFmaJnaEYIkRWlSr1AFzlvCCmi5OfovBENUYLP0MP9GtIWTOziyhvoMAToxuwzji0e1g6DGfzeD-N0ty7E7IPDu36AHw77sPZLP8R0ha3vx-QtbGPnrnAMTwuFjTAk_-Rt8eEY9y6UYXYdJByidVPaalec4fHX796vXqLnLXTZvTrNS_T908dvN7fV3dfPX24-3FWm5opUQoDjzi2ZEXTROmOkUQqclbYlinNruK2JrKkyVnIlmGgbZ5vGtYUxDQV2id4fffvdclveDn-DTvfJbyGNOoLX_yrBr_Uq7jXlgte1LAbzo4FJMefk2mmXEn0oSeeNLiXpU0ll4c3fiRN-aqXob0865NJJmyAYnydswVitmgPGjthP37nxP6H6-v6WK07YHyvktMY |
CODEN | BJPCBM |
CitedBy_id | crossref_primary_10_1038_sj_bjp_0701891 crossref_primary_10_1002_glia_22599 crossref_primary_10_1021_acs_jmedchem_8b01818 crossref_primary_10_1016_j_taap_2017_09_002 crossref_primary_10_1371_journal_pone_0205707 crossref_primary_10_1523_JNEUROSCI_6241_09_2010 crossref_primary_10_3390_separations8110222 crossref_primary_10_1046_j_1365_2680_2001_00225_x crossref_primary_10_1016_j_tips_2006_06_004 crossref_primary_10_1021_acsmedchemlett_0c00441 crossref_primary_10_1007_s00535_008_2273_7 crossref_primary_10_1021_acs_jmedchem_1c00237 crossref_primary_10_1046_j_1365_2680_2001_00201_x crossref_primary_10_1016_j_yrtph_2016_12_007 crossref_primary_10_1161_01_RES_0000238359_18495_42 crossref_primary_10_1046_j_1460_9568_2003_02753_x crossref_primary_10_1111_j_1476_5381_2011_01446_x crossref_primary_10_1002_jcp_22869 crossref_primary_10_1016_j_bcp_2004_01_020 crossref_primary_10_1038_sj_bjp_0704985 crossref_primary_10_1016_j_bbamem_2006_01_011 crossref_primary_10_1080_00498250801927427 crossref_primary_10_1177_002215540205000302 |
Cites_doi | 10.1038/sj.bjp.0701891 10.1007/978-3-642-45619-0_10 10.1007/BF00505300 10.1016/0301-0082(86)90015-8 10.1152/physrev.1990.70.3.761 10.1073/pnas.74.12.5482 10.1016/0306-3623(95)02053-5 10.1161/01.RES.63.1.97 10.1113/jphysiol.1929.sp002608 10.1007/BF00999402 10.1111/j.1476-5381.1985.tb16161.x |
ContentType | Journal Article |
Copyright | 1998 British Pharmacological Society 1998 INIST-CNRS Copyright 1998, Nature Publishing Group 1998 Nature Publishing Group |
Copyright_xml | – notice: 1998 British Pharmacological Society – notice: 1998 INIST-CNRS – notice: Copyright 1998, Nature Publishing Group 1998 Nature Publishing Group |
DBID | IQODW CGR CUY CVF ECM EIF NPM AAYXX CITATION 5PM |
DOI | 10.1038/sj.bjp.0701892 |
DatabaseName | Pascal-Francis Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef PubMed Central (Full Participant titles) |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef |
DatabaseTitleList | MEDLINE CrossRef |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1476-5381 |
EndPage | 741 |
ExternalDocumentID | 10_1038_sj_bjp_0701892 9690865 2334895 BPH5850 |
Genre | article Research Support, Non-U.S. Gov't Journal Article Comparative Study |
GroupedDBID | --- .3N .55 .GJ 05W 0R~ 1OC 23N 24P 2WC 31~ 33P 36B 3O- 3SF 3V. 4.4 52U 52V 53G 5GY 6J9 7RV 7X7 8-0 8-1 88E 8AO 8FE 8FH 8FI 8FJ 8R4 8R5 8UM A00 AAESR AAEVG AAHHS AANLZ AAONW AASGY AAXRX AAZKR ABCUV ABDBF ABPVW ABQWH ABUWG ABXGK ACAHQ ACCFJ ACCZN ACFBH ACGFO ACGFS ACGOF ACMXC ACPOU ACPRK ACXBN ACXQS ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADOZA ADXAS ADZMN ADZOD AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEUQT AEUYR AFBPY AFFPM AFGKR AFKRA AFPWT AFRAH AFZJQ AHBTC AHMBA AIACR AIAGR AITYG AIURR AIWBW AJBDE ALAGY ALIPV ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB AOIJS ATUGU AZBYB AZVAB B0M BAFTC BAWUL BBNVY BENPR BFHJK BHBCM BHPHI BKEYQ BMXJE BPHCQ BRXPI BVXVI C45 CAG CCPQU COF CS3 DCZOG DIK DRFUL DRMAN DRSTM DU5 E3Z EAD EAP EAS EBC EBD EBS ECV EJD EMB EMK EMOBN ENC ESX EX3 F5P FUBAC FYUFA G-S GODZA GX1 H.X HCIFZ HGLYW HMCUK HYE HZ~ J5H KBYEO LATKE LEEKS LH4 LITHE LK8 LOXES LSO LUTES LW6 LYRES M1P M7P MEWTI MK0 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM MY~ N9A NAPCQ NF~ O66 O9- OIG OK1 OVD P2P P2W P4E PQQKQ PROAC PSQYO Q.N Q2X QB0 RIG ROL RPM RWI SJN SUPJJ SV3 TEORI TR2 TUS UKHRP UPT WBKPD WH7 WHWMO WIH WIJ WIK WIN WOHZO WOW WVDHM WXSBR X7M XV2 Y6R YHG ZGI ZXP ZZTAW ~8M ~S- 08R AAJUZ AAPBV AAUGY AAVGM ABCVL ABHUG ABPTK ABWRO ACXME ADAWD ADDAD AFVGU AGJLS IQODW ZA5 CGR CUY CVF ECM EIF NPM AAYXX CITATION 5PM |
ID | FETCH-LOGICAL-c4580-66ae5eeb3c612fecc7c88aed7df0855dc5d407418cd758636f9ed99efaedc91a3 |
IEDL.DBID | RPM |
ISSN | 0007-1188 |
IngestDate | Tue Sep 17 21:07:09 EDT 2024 Fri Aug 23 00:35:52 EDT 2024 Sat Sep 28 07:35:27 EDT 2024 Sun Oct 29 17:09:45 EDT 2023 Sat Aug 24 00:56:54 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 4 |
Keywords | Antianginal agent Heart Adenosine Sinus node Coronary vasodilator agent Rodentia Dipyridamole Molecular interaction Vertebrata Biological fixation Mammalia Guinea pig Animal Atrioventricular node Circulatory system Adenosine receptor Mechanism of action |
Language | English |
License | CC BY 4.0 |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c4580-66ae5eeb3c612fecc7c88aed7df0855dc5d407418cd758636f9ed99efaedc91a3 |
OpenAccessLink | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0701892 |
PMID | 9690865 |
PageCount | 13 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_1565447 crossref_primary_10_1038_sj_bjp_0701892 pubmed_primary_9690865 pascalfrancis_primary_2334895 wiley_primary_10_1038_sj_bjp_0701892_BPH5850 |
PublicationCentury | 1900 |
PublicationDate | June 1998 |
PublicationDateYYYYMMDD | 1998-06-01 |
PublicationDate_xml | – month: 06 year: 1998 text: June 1998 |
PublicationDecade | 1990 |
PublicationPlace | Oxford, UK |
PublicationPlace_xml | – name: Oxford, UK – name: Basingstoke – name: England |
PublicationTitle | British journal of pharmacology |
PublicationTitleAlternate | Br J Pharmacol |
PublicationYear | 1998 |
Publisher | Blackwell Publishing Ltd Nature Publishing |
Publisher_xml | – name: Blackwell Publishing Ltd – name: Nature Publishing |
References | 1972; 8 1970; 267 1994a; 112 1986; 26 1987 1986 1994b; 112 1977; 74 1985; 84 1988; 63 1991 1981; 316 1998; 124 1996; 27 1929; 68 1993; 110 1990; 70 1969; 167 e_1_2_6_10_1 Meester B.J. (e_1_2_6_11_1) 1993; 110 Dohring H.J. (e_1_2_6_5_1) 1986 e_1_2_6_9_1 e_1_2_6_8_1 Roos H. (e_1_2_6_17_1) 1972; 8 e_1_2_6_4_1 e_1_2_6_7_1 e_1_2_6_6_1 Blum‐Kaelin D. (e_1_2_6_3_1) 1991 e_1_2_6_14_1 e_1_2_6_2_1 Meester B.J. (e_1_2_6_13_1) 1994; 112 e_1_2_6_18_1 Wauld D.R. (e_1_2_6_19_1) 1969; 167 e_1_2_6_15_1 Meester B.J. (e_1_2_6_12_1) 1994; 112 e_1_2_6_16_1 |
References_xml | – volume: 110 start-page: 140P year: 1993 article-title: Comparison of adenosine potentiation by dipyridamole in the atrioventricular and sinoatrial nodes and atrial muscle of the guinea pig publication-title: Br. J. Pharmacol. – year: 1986 – volume: 124 start-page: 685 year: 1998 end-page: 692 article-title: Comparative pharmacological analysis of adenosine receptors in the sinoatrial and atrioventricular nodes of the guinea‐pig publication-title: Br. J. Pharmacol. – volume: 112 start-page: 582P year: 1994b article-title: Potentiating interaction between adenosine and 5‐N‐ethylcarboxamidoadenosine in the guinea‐pig atrioventricular node publication-title: Br. J. Pharmacol. – volume: 316 start-page: 89 year: 1981 end-page: 95 article-title: A pharmacological method to estimate the pKI of competitive inhibitors of agonist uptake processes in isolated tissues publication-title: Naunyn-Schmiedeberg's Arch. Pharmacol. – volume: 167 start-page: 140 year: 1969 end-page: 141 article-title: A quantitative model for the effect of a saturable uptake on the slope of the dose‐response curve publication-title: J. Pharmacol. Exp. Ther. – volume: 63 start-page: 97 year: 1988 end-page: 116 article-title: Atrioventricular nodal accommodation in isolated guinea pig hearts: Physiological significance and role of adenosine publication-title: Circ. Res. – volume: 27 start-page: 613 year: 1996 end-page: 620 article-title: Adenosine transporters publication-title: Gen. Pharmacol. – volume: 112 start-page: 580P year: 1994a article-title: Classification of adenosine A1 receptors by agonist potency orders in the sinoatrial and atrioventricular nodes of the guinea‐pig publication-title: Br. J. Pharmacol. – volume: 84 start-page: 779 year: 1985 end-page: 785 article-title: Pharmacological analysis of β‐adrenoceptor‐mediated agonism in the guinea‐pig, isolated, right atrium publication-title: Br. J. Pharmacol. – volume: 68 start-page: 213 year: 1929 end-page: 237 article-title: The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart publication-title: J. Physiol. – volume: 70 start-page: 761 year: 1990 end-page: 845 article-title: Cardiovascular purinoceptors publication-title: Physiol. Rev. – volume: 26 start-page: 179 year: 1986 end-page: 209 article-title: Adenosine receptors and calcium: basis for proposing a third (A3) adenosine receptor publication-title: Prog. Neurobiol. – year: 1991 – volume: 267 start-page: 189 year: 1970 end-page: 194 article-title: Inhibition of cyclic‐3′5′‐nucleotide‐phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs publication-title: Naunyn-Schmiedeberg's Arch. Pharmacol. – volume: 8 start-page: 417 year: 1972 end-page: 425 article-title: Kinetics of adenosine uptake by erythrocytes, and the influence of dipyridamole publication-title: Mol. Pharmacol. – volume: 74 start-page: 5482 year: 1977 end-page: 5486 article-title: Two distinct adenosine‐sensitive sites on adenylate cyclase publication-title: Proc. Natl. Acad. Sci. U.S.A. – start-page: 118 year: 1987 end-page: 129 – volume-title: The Isolated Perfused Heart According to Langendorff year: 1986 ident: e_1_2_6_5_1 contributor: fullname: Dohring H.J. – ident: e_1_2_6_14_1 doi: 10.1038/sj.bjp.0701891 – ident: e_1_2_6_4_1 doi: 10.1007/978-3-642-45619-0_10 – ident: e_1_2_6_8_1 doi: 10.1007/BF00505300 – volume-title: Adrenoceptors: Structure, Mechanism, Function year: 1991 ident: e_1_2_6_3_1 contributor: fullname: Blum‐Kaelin D. – ident: e_1_2_6_16_1 doi: 10.1016/0301-0082(86)90015-8 – volume: 8 start-page: 417 year: 1972 ident: e_1_2_6_17_1 article-title: Kinetics of adenosine uptake by erythrocytes, and the influence of dipyridamole publication-title: Mol. Pharmacol. contributor: fullname: Roos H. – ident: e_1_2_6_15_1 doi: 10.1152/physrev.1990.70.3.761 – ident: e_1_2_6_10_1 doi: 10.1073/pnas.74.12.5482 – ident: e_1_2_6_18_1 doi: 10.1016/0306-3623(95)02053-5 – volume: 110 start-page: 140P year: 1993 ident: e_1_2_6_11_1 article-title: Comparison of adenosine potentiation by dipyridamole in the atrioventricular and sinoatrial nodes and atrial muscle of the guinea pig publication-title: Br. J. Pharmacol. contributor: fullname: Meester B.J. – ident: e_1_2_6_7_1 doi: 10.1161/01.RES.63.1.97 – volume: 167 start-page: 140 year: 1969 ident: e_1_2_6_19_1 article-title: A quantitative model for the effect of a saturable uptake on the slope of the dose‐response curve publication-title: J. Pharmacol. Exp. Ther. contributor: fullname: Wauld D.R. – ident: e_1_2_6_6_1 doi: 10.1113/jphysiol.1929.sp002608 – ident: e_1_2_6_9_1 doi: 10.1007/BF00999402 – volume: 112 start-page: 582P year: 1994 ident: e_1_2_6_13_1 article-title: Potentiating interaction between adenosine and 5‐N‐ethylcarboxamidoadenosine in the guinea‐pig atrioventricular node publication-title: Br. J. Pharmacol. contributor: fullname: Meester B.J. – volume: 112 start-page: 580P year: 1994 ident: e_1_2_6_12_1 article-title: Classification of adenosine A1 receptors by agonist potency orders in the sinoatrial and atrioventricular nodes of the guinea‐pig publication-title: Br. J. Pharmacol. contributor: fullname: Meester B.J. – ident: e_1_2_6_2_1 doi: 10.1111/j.1476-5381.1985.tb16161.x |
SSID | ssj0014775 |
Score | 1.7210886 |
Snippet | Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and... 1. Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and... |
SourceID | pubmedcentral crossref pubmed pascalfrancis wiley |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
StartPage | 729 |
SubjectTerms | Adenosine - antagonists & inhibitors Adenosine - metabolism Adenosine - pharmacology adenosine receptor adenosine uptake Adenosine-5'-(N-ethylcarboxamide) - pharmacology Animals Antianginal agents. Coronary vasodilator agents Atrioventricular node Atrioventricular Node - drug effects Atrioventricular Node - metabolism Atrioventricular Node - physiology Biological and medical sciences Cardiovascular system Dipyridamole - pharmacology Drug Synergism Guinea Pigs Heart Rate - drug effects In Vitro Techniques Male Medical sciences Models, Cardiovascular Pharmacology. Drug treatments Receptors, Purinergic P1 - drug effects Receptors, Purinergic P1 - physiology sinoatrial node Sinoatrial Node - drug effects Sinoatrial Node - metabolism Sinoatrial Node - physiology |
Title | Pharmacological analysis of the activity of the adenosine uptake inhibitor, dipyridamole, on the sinoatrial and atrioventricular nodes of the guinea‐pig |
URI | https://onlinelibrary.wiley.com/doi/abs/10.1038%2Fsj.bjp.0701892 https://www.ncbi.nlm.nih.gov/pubmed/9690865 https://pubmed.ncbi.nlm.nih.gov/PMC1565447 |
Volume | 124 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9wwEB6ygUKglL5C3TZBh5Je7N3V-iUd29B0KaTsIYG9GVmPxNusbfZx2H-Sn5uR_MhuL4XeLCRLwjOyvpFmvgH4YiE1rjQdGG54EIU5DRiVeTAWScIZ4xOq7Dnk9e9kehv9msfzI4i7WBjntC_zYlg-LIdlce98K-ulHHV-YqPZ9SXaHHEUpaMBDNIw7Ez09uogStMmbYFlP6SMdUyNIRutF8N8UQ9RyynO4gRecLQNmd1X9vakl7VY4-cxTV6LvY3pb6fJfTDrdqOr1_CqhZHkWzPdN3Cky7dwMWt4qHc-uXkOq1r75ILMnhmqd-_gca9ohURES01CKkMQERIb7WCTSvRlZTnFEZCSbb0RfzQpyvsix5_ByieqqHerQoll9aB9UpXuBWxbCZcRBPtWxD5W1rPSHTeKFSkrpfvR7rbYswjq4u493F79uLmcBm2KhkBGMUPDMxE61miQS0RKBtUhlYwJrVJlrAOckrGKLGhhUqFhkoSJ4Vpxrg22kZyK8BSOy6rUH4CosbA0kjSn3EQqkYyOFcslSwXLo4niHnzthJTVDRNH5m7QQ5atFxkKNmsF68HZgQz75hMbdsxjD04bUfYVrR54kB7IuK-3HNyHNaiajou7VUUPfKcN_5hZ9n02Rfts_PG_B_oEJ01UpD0H-gzHm9VWnyEs2uTnMPg5p-duMTwBqIISuQ |
link.rule.ids | 230,315,733,786,790,891,27955,27956,53825,53827 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB6VIkQlxLMVKRR8QOWSZDebl32EimqBbrWHLeotcmynzbabRPs4bH8JP5ex8-huLwhusez4EX-OZ-yZbwA-aZEaV5pyMpYxJ_BTz6GeSJ0-jyJGKRt4Up9Djs6j4UXw4zK83IGw9YUxRvsizd3iduYW-bWxraxmotfaifXGoxPUOcIgiHuP4DGu10HYKunN5UEQx3XgAs1_6FHacjX6tLeYuum0chHnHvZjD54w1A6p3lk2dqVnFV_gB8rqyBYbW9NDs8lNcdbsR6cv4Fc7ktoM5cZdLVNX3D0gefznob6E542ESr7U2a9gRxWv4XhcU1yvbTK599ha2OSYjO_Jr9dv4PdGUs8_4Q3rCSkzgsIm0Y4UOl5Fl5aarhxlXbKqlvxGkby4zlP8z8xtIvNqPc8ln5W3yiZlYV7AsiU3wUawbkn0Y6mNNs1JJp-TopSqa-1qhTVzp8qv9uHi9NvkZOg00R8cEYQUddqIq1Chri9QCMsQabGglCsZy0zb1kkRykDLQ1RI1HkiP8qYkoypDMsI5nH_AHaLslBvgcg-1wyVXuqxLJCRoF5f0lTQmNM0GEhmwed29pOqJvlIzOW8T5PFNEHEJA1iLDjaAkdXfKA9mllowUGNkS6jAZgF8RZ4unxN772dg1AwNN_N1FtgG5j9pWfJ1_EQVb_-4X839BGeDiejs-Ts-_nPd7BXO1_q46b3sLucr9QRSl_L9INZa38AxVIzvg |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Jb9QwFLagCFSpYq9IoeADKpcsk8lmH6EwGpZWObRSxSVyvLSZdpJolsPwS_i5PDtLM70g9RbLL46dfI7fs9_7HkIftUoNM006iirqhEHuO8TnuTNicUwJoWNf6H3Ik9N4eh7-uIguBqm-jNM-zwu3vJm7ZXFlfCvrOfc6PzEvPTkGmyMKw8SrhfIeokcwZ8dJZ6i3BwhhkjTJCzQHok9Ix9cYEG85c_NZ7QLWfejLLnpMwUIkenUZrEx7NVvCS1JNdovB8nTXdXKo0po1afIM_e5G07iiXLvrVe7yP3eIHu813Ofoaaup4s-NyAv0QJYv0VHaUF1vbHx2G7m1tPERTm9JsDev0N9BUeMAs5b9BFcKg9KJdUCFzlvRl4WmLQedF6_rFbuWuCivihz-Nwsbi6LeLArB5tWNtHFVmhtAtmIm6Qi0LbC-rLTzptnRZAtcVkL2T7tcQ8vMqYvL1-h88u3seOq0WSAcHkYEbNuYyUiCzc9BGVOAuIQTwqRIhNI-doJHItR6EeECbJ84iBWVglKpQIZTnwX7aKesSvkGYTFimqnSz32qQhFz4o8EyTlJGMnDsaAW-tQhIKsbso_MHNIHJFvOMkBN1qLGQodbAOnFxzqymUYW2m9w0le0ILNQsgWgvl7TfG_XABwM3Xf7-S1kG6j9p2fZl3QKJuDo4N4P-oCepF8n2a_vpz_fot0mBlPvOr1DO6vFWh6CErbK35vp9g8siDY- |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmacological+analysis+of+the+activity+of+the+adenosine+uptake+inhibitor%2C+dipyridamole%2C+on+the+sinoatrial+and+atrioventricular+nodes+of+the+guinea%E2%80%90pig&rft.jtitle=British+journal+of+pharmacology&rft.au=Meester%2C+B+J&rft.au=Shankley%2C+N+P&rft.au=Welsh%2C+N+J&rft.au=Meijler%2C+F+L&rft.date=1998-06-01&rft.issn=0007-1188&rft.eissn=1476-5381&rft.volume=124&rft.issue=4&rft.spage=729&rft.epage=741&rft_id=info:doi/10.1038%2Fsj.bjp.0701892&rft.externalDBID=n%2Fa&rft.externalDocID=10_1038_sj_bjp_0701892 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0007-1188&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0007-1188&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0007-1188&client=summon |