The determination of receptor constants for histamine H2-agonists in the guinea-pig isolated right atrium using an irreversible H2-antagonist.
From measurements of chronotropy in the guinea-pig isolated right atrium, a compound (E1309) was found which behaved as an irreversible antagonist at the histamine H2 receptor. E1309 was used to block irreversibly a proportion of the H2 receptors and the dissociation constants, relative efficacies and receptor reserves of four H2-agonists were determined. The calculated dissociation constants were similar to the Ki values reported from H2-radioligand binding studies but different from the observed EC50 values. The order of potency for the four H2-agonists was impromidine much greater than histamine greater than dimaprit greater than 4-methylhistamine. The order of relative efficacy was 4-methylhistamine greater than dimaprit greater than histamine greater than impromidine, the natural agonist not being the most efficacious. This atypical finding is discussed in relation to other receptor classes.
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D000818:Animals; D017259:Dimaprit; D004305:Dose-Response Relationship, Drug; D005260:Female; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*; D013890:Thiourea / Q000502:physiology
D006146:Guanidines; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D011943:Receptors, Adrenergic, beta; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D013844:Thiazoles; C025566:4-methylhistamine; D006632:Histamine; C048485:E 1309; D017446:Impromidine; D013890:Thiourea; D017259:Dimaprit