The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A2 activator, in normotensive rats

Altinbas B., Topuz B. B., Yilmaz M. S., AYDIN C., SAVCI V., Jochem J., ...More

Prostaglandins Leukotrienes and Essential Fatty Acids, vol.87, pp.153-158, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 87
  • Publication Date: 2012
  • Doi Number: 10.1016/j.plefa.2012.08.006
  • Journal Name: Prostaglandins Leukotrienes and Essential Fatty Acids
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.153-158
  • Keywords: Brain phospholipase A(2), Melittin, Mean arterial pressure, Heart rate, Central histaminergic system, Intracerebroventricular, Microdialysis, CRITICAL HEMORRHAGIC HYPOTENSION, CENTRAL CARDIOVASCULAR REGULATION, CENTRAL CHOLINERGIC SYSTEM, THROMBOXANE A2 ANALOG, INDUCED REVERSAL, ADMINISTERED HISTAMINE, ARACHIDONIC-ACID, INVOLVEMENT, U-46619, SHOCK
  • Bursa Uludag University Affiliated: Yes


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 A2. Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A2 (TXA2) 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 2nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H2 receptor antagonist ranitidine (50nmol; i.c.v.) almost completely and H3/H4 receptor antagonist thioperamide (50nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H1 receptor blocker chlorpheniramine (50nmol; 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. © 2012 Elsevier Ltd.