Alteration of histamine response by H2-receptor antagonism in the guinea pig

1980 ◽  
Vol 48 (4) ◽  
pp. 613-618 ◽  
Author(s):  
J. M. Drazen ◽  
C. S. Venugopalan ◽  
M. W. Schneider
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Fold Increase ◽  
H2 Receptor Antagonist ◽  
Receptor Antagonism ◽  
H2 Receptor ◽  
H2 Receptors ◽  
Histamine Response

Effects of H2-receptor antagonism on the response to histamine was studied in the guinea pig in vivo and in vitro. The H2-receptor antagonist, metiamide (100 micro M), resulted in an enhanced histamine response in eight of eight parenchymal strips and in four of eight tracheal spirals. On the average the parenchymal strips were 20-fold more sensitive to histamine (P less than 0.001), whereas the tracheal spirals demonstrated an insignificant, 20%, increase in sensitivity after metiamide treatment. These results are consistent with the hypothesis that there are inhibitory H2-receptors in guinea pig airways and they predominate in the periphery. When we determined the effects of H2-antagonism on the histamine response in vivo we found that the histamine response was enhanced only in animals that had been treated with the beta-receptor antagonist propranolol. In these animals there was a mean 2.2-fold increase in histamine sensitivity. These results suggest that although there are inhibitory H2-receptors in the guinea pig lung, their role in modulating the in vivo response is much less than beta-adrenergic mechanisms.

Role of histamine H1- and H2-receptors in myoelectric activity of small bowel in the dog

1980 ◽  
Vol 238 (1) ◽  
pp. G50-G56
Author(s):  
S. J. Konturek ◽  
R. Siebers
Keyword(s):  
Small Bowel ◽  
Receptor Antagonist ◽  
Intestinal Motility ◽  
Receptor Agonist ◽  
Physiological Role ◽  
Myoelectric Activity ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
H2 Receptor ◽  
H2 Receptors

Studies were conducted in conscious dogs implanted with monopolar silver electrodes along the small intestine to determine whether the intestinal motility response to histamine is mediated by H1-receptors alone or whether H2-receptors are also involved in the response. Histamine infusion alone induced a marked increase in the appearance rate and the propagation velocity of the interdigestive myoelectric complexes (IMC). This effect was reproduced by the administration of the selective H1-receptor agonist, 2-methylhistamine, and abolished by the H1-receptor antagonist, tripelennamine. Tripelennamine alone decreased the frequency of occurrence of the IMC in fasted animals and reduced significantly the spike potential activity of the small bowel in fed dogs. Neither the H2-receptor agonist, dimaprit, nor the H2-receptor antagonist, metiamide, had any influence on the motility patterns in fasted or fed animals. We conclude that histamine influences the patterns of small bowel motility via stimulation of H1-receptors but its physiological role in modulating intestinal motility remains to be determined.

Effect of a histamine H2-receptor antagonist on immunologically induced mediator release in vitro

1974 ◽  
Vol 4 (5) ◽  
pp. 297-303 ◽  
Author(s):  
L. W. Chakrin ◽  
R. D. Krell ◽  
J. Mengel ◽  
D. Young ◽  
C. Zaher ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mediator Release ◽  
H2 Receptor Antagonist ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Release In Vitro ◽  
Histamine H2 Receptor Antagonist

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist

1989 ◽  
Vol 67 (9) ◽  
pp. 989-993 ◽  
Author(s):  
A. W. Ford-Hutchinson ◽  
Y. Girard ◽  
A. Lord ◽  
T. R. Jones ◽  
M. Cirino ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Competitive Inhibition ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Prostaglandin Endoperoxide ◽  
Induced Aggregation

L-670,596 ((−)6,8-difluoro-9-p-methylsulfonyl benzyl-1,2,3,4-tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 × 10−9 M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 × 10−7 M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U-44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1–5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.Key words: thromboxane A2, thromboxane antagonist, prostaglandin endoperoxides, platelet aggregation.

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