Effect of phospholipase A2 activation on the receptor function in the rat left atrium: unmasking of a positive inotropic effect of methacholine.
1. To elucidate the functional consequence of endogenous phospholipase A2 activation, the effect of pretreatment with melittin on (-)-isoprenaline, forskolin and methacholine inotropic responses in isolated rat left atria was studied. 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. 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 A2 inhibitor. 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. It is suggested that the combination of mepacrine/melittin abolishes the activity of an inhibitory G protein.
Kramer
K
K
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Faculty of Chemistry, Vrije University, The Netherlands.
Smink
C G
CG
Bast
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D017981:Receptors, Neurotransmitter; D016210:Methacholine Chloride; D005576:Colforsin; D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D007545:Isoproterenol