Histamine receptors in brain vessels of guinea-pig: in-vitro pharmacology and ligand binding.

The subtype of histamine receptors in brain vessels of guinea-pig has been characterized by ligand binding and in-vitro pharmacology using selective antagonists. In the basilar artery histamine caused a concentration-related contraction with an EC50 of 1.6 +/- 0.3 microM. H1-receptor blockade with mepyramine and chlorpheniramine caused a displacement to the right of the histamine concentration-response curve with an apparent KD of 0.4 and 4.6 nM respectively, whereas H2-receptor blockade with cimetidine was without effect. Histamine did not induce any dilatory responses of vessels procontracted by 60 mM potassium-containing buffer in the presence or absence of histamine antagonists. Ligand-binding studies with [3H]mepyramine yielded a KD value of 5.5 nM in pial vessel membranes and 1.7 nM in the choroid plexus, confirming the presence of H1-receptors. Nimodipine caused a concentration-related blockade of histamine-induced contractions. Omission of Ca2+ from the extracellular medium for 30 min reduced the contractile responses to histamine in the basilar artery by 96%. Subsequent addition of Ca2+ caused concentration-related contractions which were inhibited by nimodipine. Thus, the histamine H1-receptor activation in guinea-pig basilar artery is coupled to dihydropyridine-sensitive Ca2+ channels.