The involvement of the central cholinergic system in the pressor and bradycardic effects of centrally administrated melittin in normotensive conscious rats

Abstract

Recently we demonstrated that centrally administrated melittin, a phospholipase A(2) (PLA(2)) activator, caused pressor and bradycardic effect in the normotensive conscious rats. In the current study we aimed to determine the mediation of central cholinergic system in the pressor and bradycardic effect of centrally administrated melittin. Studies were performed in normotensive male Sprague-Dawley rats. 1.5, 3.0 or 6.0 mu g/5.0 mu l doses of melittin were injected intracerebroventricularly (i.c.v.). Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR). In order to test the mediation of central cholinergic system on the pressor and bradycardic effect of melittin, the rats were pretreated with mecamylamine (50 mu g; i.c.v.), cholinergic nonselective nicotinic receptor antagonist, atropine sulfate (10 mu g; i.c.v.), a cholinergic nonselective muscarinic receptor antagonist, hemicholinium-3 (20 mu g; i.c.v.), a high affinity neuronal choline uptake inhibitor, methyllycaconitine (10 and 25 mu g; i.c.v.) or alpha-bungarotoxin (10 and 25 mu g; i.c.v.), selective antagonists of alpha-7 subtype nicotinic acetylcholine receptors (alpha 7nAChRs), 15 min prior to melittin (3.0 mu g) injection. Pretreatment with mccamylamine, hemicholinium-3, methyllycaconitine or alpha-bungarotoxin partially attenuated the pressor and bradicardia effect of elicited by melittin in the normotensive conscious rats whereas pretreatment with atropine had no effect. In conclusion, i.c.v. administration of melittin increases MAP and decreases HR in conscious rats. The activation of central nicotinic cholinergic receptors, predominantly alpha 7nAChRs, partially acts as a mediator in the pressor responses to i.c.v. injection of melittin in the normotensive conscious rats. Moreover, decreased uptake of choline to the cholinergic terminals may consider that melittin activates central choline and acetylcholine release, as well.