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Research ArticleArticle

Regulation of Adenylyl Cyclase Type V/VI in Smooth Muscle: Interplay of Inhibitory G Protein and Ca2+ Influx

Karnam S. Murthy and Gabriel M. Makhlouf
Molecular Pharmacology July 1998, 54 (1) 122-128; DOI: https://doi.org/10.1124/mol.54.1.122
Karnam S. Murthy
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Gabriel M. Makhlouf
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Abstract

The characteristics of inhibitory regulation of adenylyl cyclase V/VI by Ca2+ and G proteins were examined in dispersed gastric smooth muscle cells. The mechanisms were evoked separately, sequentially, or concurrently using ligand-gated and G protein-coupled receptor agonists and receptor-independent probes (e.g, thapsigargin). During the initial phase of agonist stimulation, α,β-methylene-ATP, UTP, and ATP inhibited forskolin-stimulated cAMP formation in a concentration-dependent fashion. Inhibition by α,β-methylene-ATP, which activates ligand-gated P2X receptors, was abolished by zero Ca2+, whereas inhibition by UTP, which activates P2Y2 receptors coupled to Gq/11 and Gi3, was not affected by zero Ca2+ but was abolished by pertussis toxin (PTX). Inhibition by ATP, which activates both P2X and P2Y2 receptors, was not affected by zero Ca2+ alone; but after inhibition mediated by Gαi3 was blocked with PTX, inhibition by Ca2+influx was unmasked and was abolished by zero Ca2+. Inhibition by cholecystokinin-8 was observed only during the phase of capacitative Ca2+ influx and was blocked by zero Ca2+. Inhibition by UTP during this phase was not affected by zero Ca2+ alone; but after inhibition mediated by Gαi3 was blocked with PTX, inhibition by Ca2+influx was unmasked and was abolished by zero Ca2+. Inhibition of adenylyl cyclase V/VI activity in smooth muscle can be mediated independently by inhibitory G proteins and Ca2+influx but is exclusively mediated by inhibitory G proteins when both mechanisms are triggered.

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Molecular Pharmacology: 54 (1)
Molecular Pharmacology
Vol. 54, Issue 1
1 Jul 1998
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Research ArticleArticle

Regulation of Adenylyl Cyclase Type V/VI in Smooth Muscle: Interplay of Inhibitory G Protein and Ca2+ Influx

Karnam S. Murthy and Gabriel M. Makhlouf
Molecular Pharmacology July 1, 1998, 54 (1) 122-128; DOI: https://doi.org/10.1124/mol.54.1.122

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Research ArticleArticle

Regulation of Adenylyl Cyclase Type V/VI in Smooth Muscle: Interplay of Inhibitory G Protein and Ca2+ Influx

Karnam S. Murthy and Gabriel M. Makhlouf
Molecular Pharmacology July 1, 1998, 54 (1) 122-128; DOI: https://doi.org/10.1124/mol.54.1.122
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