title: The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A2 activator, in normotensive rats.
abstract: Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A(2). Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A(2) (TXA(2)) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2 nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H(2) receptor antagonist ranitidine (50 nmol; i.c.v.) almost completely and H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H(1) receptor blocker chlorpheniramine (50 nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, 16059 Bursa, Turkey.
authors.forename: Burcin
authors.initials: B
authors.lastname: Altinbas
authors.forename: Bora B
authors.initials: BB
authors.lastname: Topuz
authors.forename: Mustafa S
authors.initials: MS
authors.lastname: Yilmaz
authors.forename: Cenk
authors.initials: C
authors.lastname: Aydin
authors.forename: Vahide
authors.initials: V
authors.lastname: Savci
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jochem
authors.forename: Sami
authors.initials: S
authors.lastname: Aydin
authors.forename: Murat
authors.initials: M
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008555:Melitten / Q000008:administration & dosage* / Q000494:pharmacology*; D017551:Microdialysis; D054467:Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008555:Melitten; D054467:Phospholipases A2