Bradykinin inhibits cyclic AMP accumulation in D384-human astrocytoma cells via a calcium-dependent inhibition of adenylyl cyclase

• Published in: Cellular signalling Vol. 5; no. 3; pp. 279 - 288
• Main Authors: Altiok, Nedret, Fredholm, Bertil B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.1993; Elsevier
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Adenosine - analogs & derivatives; Adenosine - antagonists & inhibitors; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide); Adenylyl Cyclase Inhibitors; astrocyte; Astrocytoma - metabolism; Biological and medical sciences; Bradykinin - pharmacology; Brain Neoplasms - metabolism; Calcimycin - pharmacology; Calcium - physiology; Calcium entry; calcium stores; calmodulin; Calmodulin - metabolism; Cell physiology; Colforsin - antagonists & inhibitors; Colforsin - pharmacology; Cyclic AMP - metabolism; Dopamine - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Fundamental and applied biological sciences. Psychology; Hormonal regulation; Humans; Hydroquinones - pharmacology; Inositol 1,4,5-Trisphosphate - physiology; Molecular and cellular biology; Neoplasm Proteins - antagonists & inhibitors; phosphodiesterase; Pyrrolidinones - pharmacology; Rolipram; Signal Transduction - drug effects; Tumor Cells, Cultured; W-7; Calcium entry; IBMX; calcium stores; tBuBHQ-2,5-di(tert-butyl)-1,4-benzohydroquinone; calmodulin; CaM; EGTA; PDE; NECA; DDT; IP 3; phosphodiesterase; astrocyte; BAPTA-AM; Human; Cell culture; Calcium; Radiolabelling; Enzyme; Peptide hormone; Phosphorus-oxygen lyases; Cyclic AMP; Lyases; Astrocyte; Neuropeptide; Fluorescence spectrometry; Adenylate cyclase; Signal transduction; Cell line; Enzymatic activity; Bradykinin; Plasma membrane; Tumor; Inhibition
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/0898-6568(93)90018-H

Bradykinin causes a concentration-dependent, transient rise in intracellular Ca 2+ and a sustained inhibition of forskolin-, dopamine- and 5′- N-ethyl-carboxamidoadenosine (NECA)-stimulated cAMP accumulation in D384 astrocytoma cells. Chelation of intracellular calcium abolished bradykinin's inhibitory effect on cAMP accumulation. Chelating extracellular Ca 2+ did not block the initial, but eliminated the sustained inhibition of cAMP accumulation. Increasing Ca 2+ influx by calcium ionophore A23187 caused a concentration-dependent inhibition of stimulated cAMP accumulation. A hydroquinone derivative 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), which inhibits microsomal Ca 2+ sequestration, did not mimic the effect of bradykinin, although it increased [Ca 2+] i even more than A23187 did. The inhibitory effect of bradykinin was not mediated by Ca 2+/CaM-dependent stimulation of phosphodiesterase (PDE). Forskolin-stimulated adenylyl cyclase activity was inhibited by Ca 2+ (10 −7 to 10 −3 M), both in ethyleneglycol-bis-( β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA) washed and native D384 plasma membranes. This effect was not altered by calmodulin (CaM) or CaM-antagonists. Bradykinin treatment, which attenuates cAMP accumulation in intact cells, did not do so in plasma membranes. These findings suggest that bradykinin-induced inhibition of cAMP formation in D384 cells requires mobilization of [Ca 2+] i and subsequent entry of Ca 2+ which directly interacts with a component of the adenylyl cyclase system.