The effect of phospholipase C on the responsiveness of cardiac receptors. II. The specificity of phospholipase C inhibition of receptor-mediated responses

To determine if phospholipids play a role in receptor-mediated responses of the heart to inotropic and chronotropic agents, a crude preparation of phospholipase C (PLC) from Clostridium perfringens was used to perturb membrane lipids in the isolated spontaneously beating 5-day-old embryonic chick heart. Its inotropic responsiveness to acetylcholine (AcCh) and 4-methylhistamine (4-MeH) was established in the field-stimulated preparation. The inotropic responses to AcCh, angiotensin II (A II) and 4-MeH were inhibited by PLC treatment in the spontaneously beating preparation. However, such pretreatment had no effect on the chronotropic responses to AcCh or 4-MeH. The inotropic response to calcium was not altered by pretreatment with PLC, indicating that PLC does not affect the capacity of the tissue to respond to an agent whose inotropic effect is not receptor mediated. Ultrastructural changes, as determined by electron microscopy, were not evident after exposure to PLC. Methacholine selectively prevented the effect of PLC on the cholinergic response, (Sar¹, Ile⁸)-A II prevented the PLC inhibition of the A II response and metiamide prevented the PLC inhibition of the 4-MeH response. Propranolol did not alter the PLC inhibition of the inotropic responses to AcCh, A II, or 4-MeH. Thus, PLC appears to affect a component or components common to and essential for the receptor-mediated responses investigated.