Cholinergic antagonism of beta-adrenergic stimulated action potentials and adenylate cyclase activity in rabbit ventricular cardiomyocytes.
The cholinergic antagonism of beta-adrenergic stimulation was examined by measuring adenylate cyclase activity and calcium-mediated action potentials in isolated ventricular cardiomyocytes of adult rabbits. The beta-adrenoceptor agonist isoproterenol and the direct adenylate cyclase activator forskolin increased adenylate cyclase activity in homogenates of the myocytes. The cholinergic agonist carbachol (10 nM-100 microM) inhibited in a concentration dependent manner basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase activity. The carbachol effect on basal adenylate cyclase activity was antagonized by atropine (10 microM). In parallel experiments using intact cardiomyocytes, calcium action potentials were elicited by intracellular depolarizing current pulses in partially depolarized preparations. These action potentials were prolonged by isoproterenol, forskolin and dibutyryl cyclic AMP. Acetylcholine reversibly inhibited the prolongation of the action potential induced by isoproterenol and forskolin but not dibutyryl cyclic AMP. These results suggest that cholinergic agonists modulate the increase in the calcium current elicited by isoproterenol and forskolin in isolated ventricular cardiomyocytes by inhibiting adenylate cyclase activity.
Watson
J M
JM
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Vogel
S M
SM
Cotterell
D J
DJ
Dubocovich
M L
ML
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D011976:Receptors, Muscarinic; D005576:Colforsin; D003994:Bucladesine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine