The effects of P1- and muscarinic-receptor agonists upon cAMP-dependent and independent inotropic responses of guinea-pig cardiac preparations.
1. The indirect negative inotropic effects of P1- and muscarinic-receptor agonists were compared by examining how the responses of isolated guinea-pig left atria and papillary muscles to positive inotropes were affected by the presence of the P1-receptor agonist, L-PIA or the muscarinic-receptor agonist, carbachol. 2. The indirect negative inotropic effects of L-PIA and carbachol were similar: both attenuated the responses of left atria more effectively than those of papillary muscles; and both more effectively attenuated responses to the cAMP-dependent positive inotropes, isoprenaline and forskolin. 3. However, there were differences: L-PIA, but not carbachol, was able at high concentrations to inhibit the responses of left atria to the calcium channel opener Bay K 8644; and at concentrations that produced similar direct negative inotropic effects, L-PIA consistently attenuated the positive inotropes more effectively than carbachol. 4. These findings are consistent with L-PIA being able to activate an additional negative inotropic mechanism that carbachol cannot.
Urquhart
R A
RA
Department of Pharmacology, Welsh School of Pharmacy, University of Wales College, Cardiff.
Broadley
K J
KJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects*
D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D005576:Colforsin; D010660:Phenylisopropyladenosine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium