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.