Characterization of histamine receptors in isolated human cerebral arteries.

1. The subtypes of histamine-receptors which mediate dilatation of small human cerebral arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilator responses were studied after preconstriction with prostaglandin F2 alpha, since contraction was not seen with histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 5.2 +/- 1.6 x 10(-8) M. 3. Mepyramine caused a parallel shift to the right of the histamine concentration-response curve whereas cimetidine was without observable effect. This suggests the presence of histamine H1-receptors only. However, combined treatment with mepyramine and cimetidine caused a more marked displacement of the concentration-response curve to the right. Schild analysis indicated that in situations of near complete blockade of either of the histamine receptor subtypes, simple competitive antagonism both at H1- and H2-receptors can be revealed with a pA2 value of 8.64 for mepyramine and a pA2 value of 6.52 for cimetidine. 4. The 'selective' H1-receptor agonists pyridylethylamine, 2-methylhistamine (2-Me-histamine) and thiazolylethylamine, and the H2-receptor agonists dimaprit, impromidine and 4-methylhistamine (4-Me-histamine) all mimicked the histamine response, but were less potent than histamine. The order of potency was thiazolylethylamine greater than dimaprit greater than impromidine greater than 2-Me-histamine greater than pyridylethylamine greater than 4-Me-histamine. 5. These results indicate that the histamine-induced dilatation in small human cerebral arteries is mediated by both H1- and H2-receptors and that the former subtype of histamine receptor predominates.