metiamide and 2-(2-aminoethyl)thiazole

Histamine H1 and H2 receptors in the rabbit isolated ovarian artery and vein were studied. Histamine (10(-6)-3 X 10(-4) M) and 2-thiazolylethylamine (2ThEA) (10(-5)-3 X 10(-4)) concentration dependently caused contraction of both vessels. The -log EC50 for the artery was 5.20 +/- 0.13 and 4.48 +/- 0.01, and for the vein it was, 5.50 +/- 0.10 and 5.10 +/- 0.27, respectively. Metiamide (10(-5) M) significantly potentiated histamine-induced but not 2ThEA-induced contractions. The pA2 for antagonism by mepyramine against histamine and 2ThEA was 8.80 +/- 0.20 (slope = 0.73) and 9.02 +/- 0.11 (slope = 0.74) in the artery and 9.50 +/- 0.30 (slope = 1.0 +/- 0.2) and 9.00 +/- 0.20 (slope = 1.0 +/- 0.1) in the vein. Histamine and impromidine concentration dependently relaxed the contracted ovarian artery and vein. Impromidine was 300-fold and sixfold more potent than histamine in the artery and vein, respectively. The relaxant potency of histamine was the same in both vessels. The relaxations were antagonized by metiamide (10(-5) M). The KB against histamine and impromidine was similar in both vessels. These results indicate that functional histamine H1 and H2 receptors exist in the ovarian artery and vein. The possible relevance of this to the proposed role of histamine in ovulation is discussed.

Topics: Animals; Arteries; Dose-Response Relationship, Drug; Female; Histamine; Imidazoles; Impromidine; Metiamide; Ovary; Rabbits; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Vasodilation; Veins

The characteristics of histamine-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in slices of rabbit cerebral cortex have been investigated. The selective H2-receptor antagonists, cimetidine, tiotidine, metiamide and ranitidine appeared to antagonize the stimulation of cyclic AMP accumulation elicited by histamine in a competitive manner consistent with an interaction with histamine H2-receptors. The H1-receptor antagonist mepyramine (0.8 microM) produced only a weak inhibition of the response to histamine. The inhibition appeared to be non-competitive producing a decrease in the maximal response with little effect on the EC50 value. The specific H2-receptor agonist, impromidine, produced a maximum response of only 31 +/- 2% of that obtained with histamine. Studies with histamine and impromidine in combination indicated that impromidine was not acting as a partial agonist. 2-Thiazolylethylamine, a selective H1-agonist, produced only a weak response (EC50 approximately 1mM) yielding a relative potency with respect to histamine (= 100) of 2.5. In the presence of a supramaximal concentration of impromidine, histamine and 2-thiazolylethylamine further elevated the response to impromidine. In these conditions the relative potency of 2-thiazolylethylamine was increased to 59 (histamine = 100), a value which was comparable with that reported for H1-receptor-mediated contractions of guinea-pig ileum. The H1-receptor antagonists mepyramine, promethazine, triprolidine and chlorpheniramine competitively antagonized the potentiation of impromidine-stimulated cyclic AMP accumulation elicited by histamine and 2-thiazolylethylamine in rabbit cerebral cortex without affecting the response to impromidine alone. (+)-Chlorpheniramine was some 150 fold more potent than the (-)-isomer in this respect. Histamine and adenosine in combination had a much greater than additive effect on the accumulation of cyclic AMP in rabbit cerebral cortical slices. The potentiation of the adenosine response could be partially but not completely antagonized by either cimetidine or mepyramine. In the presence of H2-receptor blockade with 0.02 mM tiotidine, histamine elicited a significant potentiation (EC50 44 microM) of the response to adenosine. This response was antagonized competitively by mepyramine yielding a KB value of 0.05 microM similar to that obtained from inhibition of the potentiation of impromidine-stimulated accumulation of cyclic AMP (0.02 microM). Thes

Topics: Adenosine; Animals; Cerebral Cortex; Chlorpheniramine; Cimetidine; Cyclic AMP; Dose-Response Relationship, Drug; Drug Synergism; Imidazoles; Impromidine; Kinetics; Mathematics; Metiamide; Rabbits; Ranitidine; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles