Abstract

1. 1. To elucidate the functional consequence of endogenous phospholipase A 2 activation, the effect of pretreatment with melittin on (-)-isoprenaline, forskolin and methacholine inotropic responses in isolated rat left atria was studied. 2. 2. Melittin pretreatment resulted in a significant decrease of the positive inotropic response of (-)-isoprenaline, whereas no significant change in the forskolin response was seen. 3. 3. A more prominent negative inotropic effect of methacholine could be perceived after melittin pretreatment. These effects of melittin were not simply reversed by mepacrine, a phospholipase A 2 inhibitor. 4. 4. After combined mepacrine/melittin pretreatment, a positive inotropic response was elicited by methacholine, which could be blocked by atropine but not by (+/-)-propranolol. 5. 5. It is suggested that the combination of mepacrine/melittin abolishes the activity of an inhibitory G protein.

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