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Histamine-induced cyclic AMP formation in the chick hypothalamus: interaction with vasoactive intestinal peptide
Jolanta B Zawilska1, Hanna Gendek-Kubiak, Agata Woldan-Tambor
1Department of Pharmacodynamics, Medical University, Muszyńskiego 1, PL 90-151 Łódź, Poland. jzawilska@pharm.am.lodz.pl
Abstract:
Effects of histamine (HA) on cyclic AMP production and its action upon the effects evoked by vasoactive intestinal peptide (VIP) were studied in the chick hypothalamus. HA (0.1-1000 microM) potently stimulated cyclic AMP formation in the hypothalamic slices, reaching maximal effect (2.5-3.5-fold increase) at a 100 microM concentration, and displaying an EC50 value of approximately 6.5 microM/ The stimulatory action of HA was mimicked by agonists of HA receptors, with the following rank order of potency: HA>4-methylHA (H2)>or=Nalpha,Nalpha-dimethylHA (H3>>H1=H2)>or=2-methylHA (H1)>>amthamine (H2)>>dimaprit (H2) approximately tele-methylHA. The HA (100 microM)-evoked increase in cyclic AMP production was concentration-dependently antagonized by selective H2-HA receptor blockers (aminopotentidine>>cimetidine>or=ranitidine>>zolantadine) and was not affected by mepyramine and thioperamide, a selective H1- and H3-HA receptor antagonist, respectively. The pharmacological profile of HA receptors linked to the cyclic AMP-generating system in the chick hypothalamus indicates that they represent either an avian-specific H2-like HA receptor or a novel subtype of HA receptors. Chicken VIP (cVIP; 0.1-3 microM) potently stimulated cyclic AMP synthesis in the chick hypothalamus in a concentration-dependent manner. A combination of cVIP with HA produced cyclic AMP response more than additive, and such a synergistic interaction was antagonized by ranitidine. It is suggested that in the avian brain HA and VIP may play in concert to regulate neuroendocrine processes.
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