Ca++ inhibition of isoproterenol responses in mammalian skeletal muscle

S. R. Gross, Martin Kelly

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In noncontracting mouse hemidiaphragms incubated in modified Krebs-Ringer-bicarbonate buffer with 10 mM Ca++, isoproterenol-stimulated phosphorylase a formation, conversion of phosphorylase kinase to the activated form, elevation of cyclic AMP-dependent protein kinase activity ratios and increase in cyclic AMP concentrations were reduced 35 to 50% over the responses in buffer with 2.5 mM Ca++. In buffer with 10 mM Ca++, the initial rate of isoproterenol-stimulated cyclic AMP accumulation was 59% of that in buffer with 2.5 mM Ca++. The inhibitory action of Ca++ on cyclic AMP accumulation was antagonized by verapamil, but not by inhibitors of cyclic nucleotide phosphodiesterase activity. In buffer with 2.5 mM Ca++, isoproterenol-stimulated cyclic AMP accumulation was inhibited by A23187 and caffeine, agents that can increase intracellular Ca++ concentrations. In addition to Ca++, high concentrations of Co++, Ni++, Mn++ and, to a lesser extent, Sr++ inhibited the isoproterenol response. The results of these studies indicate that high buffer Ca++ concentrations inhibit the response of the glycogenolytic pathway to isoproterenol by an action on cyclic AMP formation. The authors propose that the site of the inhibitory action of Ca++ is the divalent metal activator site associated with hormone-stimulated adenylate cyclase activity.

Original languageEnglish (US)
Pages (from-to)271-277
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume217
Issue number2
StatePublished - 1981
Externally publishedYes

Fingerprint

Isoproterenol
Cyclic AMP
Buffers
Skeletal Muscle
Phosphorylase a
Phosphorylase Kinase
Cyclic Nucleotides
Phosphoric Diester Hydrolases
Calcimycin
Verapamil
Cyclic AMP-Dependent Protein Kinases
Caffeine
Adenylyl Cyclases
Metals
Hormones

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ca++ inhibition of isoproterenol responses in mammalian skeletal muscle. / Gross, S. R.; Kelly, Martin.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 217, No. 2, 1981, p. 271-277.

Research output: Contribution to journalArticle

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