Agonist-induced desensitization of dopamine D-1 receptors in bovine retina and rat striatum
We have investigated agonist-induced desensitization of dopamine (DA) D-1 receptor mediated accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) in bovine retinas and rat striata in vitro. Tissues were exposed to various pharmacological agents for 60 min, washed and homogenized. D-1...
Saved in:
Published in | The Journal of pharmacology and experimental therapeutics Vol. 266; no. 1; pp. 350 - 357 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Pharmacology and Experimental Therapeutics
01.07.1993
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | We have investigated agonist-induced desensitization of dopamine (DA) D-1 receptor mediated accumulation of adenosine 3':5'-cyclic
monophosphate (cAMP) in bovine retinas and rat striata in vitro. Tissues were exposed to various pharmacological agents for
60 min, washed and homogenized. D-1 agonist-promoted accumulation of cAMP in the presence of adenosine 5'-triphosphate (ATP)
and 5'-guanylylimidodiphosphate (GppNHp) was then measured. Retinas and striata incubated with DA or (+) SKF 38393 (100 microM
each) displayed diminished capacities to accumulate cAMP when they were re-exposed to the same drugs. As expected, retinas
and striata treated wtih (+) SKF 38393 also showed an attenuated formation of cAMP when restimulated with DA. In addition,
D-1 receptors in retinas that had been treated with quinpirole, a D-2 agonist, did not become desensitized. Furthermore, 0.2
microM SCH 23390 prevented D-1 receptor subsensitivity caused by 100 microM DA. Interestingly, retinas and striata incubated
with forskolin, a direct stimulator of adenylyl cyclase, also displayed a diminished enzymatic response to restimulation by
the same agent, as well as by DA. Additionally, retinas incubated with 100 microM DA were refractory to forskolin-induced
cAMP formation. Finally, results of 3H-SCH 23390 binding to control and DA-treated retinas indicated that agonist treatment
did not induce significant changes in either receptor density or binding affinity. The data indicate that bovine retinas and
striatal slices in vitro are suitable to investigate various aspects of the desensitization of neuronal responses to DA D-1
agonists or forskolin. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |