dinoprost and 2-(2-aminoethyl)thiazole

1. The subtypes of histamine-receptors which mediate dilatation of small human temporal arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilatory responses were studied after preconstriction with prostaglandin F2 alpha since contraction was not seen at histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 2.8 +/- 0.6 X 10(-7) M. 3. Cimetidine caused a parallel shift to the right of the histamine concentration-response curve whereas mepyramine was without observable effect. This suggests the presence of histamine H2-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 the histamine H1-receptor subtypes, simple competitive antagonism at H2-receptors can be revealed with a pA2 value of 6.58 for cimetidine. The apparent pA2 value for mepyramine was 8.58. 4. The 'selective' H1-receptor agonists pyridylethylamine, 2-methylhistamine and thiazolylethylamine, and the H2-receptor agonists dimaprit, impromidine and 4-methylhistamine all mimicked the histamine response, but all except impromidine were less potent than histamine. The order of potency was impromidine greater than thiazolylamine greater than 4-Me-histamine greater than 2-Me-histamine greater than dimaprit greater than pyridylethylamine greater than tele-Me-histamine. 5. These results indicate that the histamine-induced dilatation in small human temporal arteries is mediated by both H1- and H2-receptors and that the latter subtype of histamine receptors predominates.

Topics: Adult; Cimetidine; Dinoprost; Female; Histamine; Humans; Imidazoles; Impromidine; In Vitro Techniques; Male; Methylhistamines; Middle Aged; Pyridines; Pyrilamine; Receptors, Histamine; Temporal Arteries; Thiazoles; Vasoconstriction; Vasodilation

1. The dog isolated sphincter pupillae contracted in response to acetylcholine, angiotensin II (AII), bradykinin, prostaglandins F2 alpha, D2, E2 and I2, and thionate thromboxane A2 (sTXA2) in a concentration-dependent manner. 2. AII-induced contractions were suppressed by treatment with saralasin, indomethacin, aspirin and diphloretin phosphate (DPP), a prostaglandin receptor antagonist. Contractions induced by bradykinin were also attenuated by indomethacin, aspirin and DPP. The amount of prostaglandin F2 alpha (PGF2 alpha) in the bathing media was increased approximately 41% following stimulation of the preparations by bradykinin. 3. The potency of contractile responses was in the order of PGF2 alpha greater than PGD2 = sTXA2 greater than PGE2 greater than arachidonic acid greater than PGI2. Contractions induced by PGF2 alpha were not significantly affected by treatment with indomethacin and ONO3708, an antagonist of the vasoconstrictor effect of prostaglandins, but appreciably attenuated by DPP. Arachidonic acid-induced contractions were inhibited by indomethacin. 4. Contractions of dog iris sphincter muscle in response to AII and bradykinin may be mediated via substances synthesized by cyclo-oxygenase from arachidonic acid. The distribution and nature of the prostaglandin receptors appear to differ markedly in iris sphincter and vascular smooth muscles.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Bradykinin; Dinoprost; Dogs; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Prostaglandins; Pupil; Thiazoles; Thromboxane A2