Alpha adrenoreceptors of rabbit aorta and stomach fundus

H. Fuder, W. L. Nelson, Duane Miller, P. N. Patil

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Stereoisomers of WB-4101, dibozane, prosympal, benzylnaphazoline, tetrahydrozoline and epinephrine were selected to probe the similarity and differences in the alpha adrenoreceptors of rabbit aorta and stomach tissues. Phenylephrine was used as an agonist and the competitive receptor blocking effects were quantitated. (S)-WB-4101 was the most potent and highly selective alpha blocker tested. The -log molar K(B) or pA2 values on aorta and fundus were 9.16 and 9.54, respectively. In both tissues, 500- to 10,000-fold higher concentration is needed to block serotonergic and histaminergic receptors, respectively. The alpha adrenoceptor blocking activity ratio for the (S)- and (R)-WB-4101 isomers in two tissues were 40- and 37-fold, respectively. The ratios are not significantly different. On the contrary, 30 μM of the benzylnaphazoline isomers depressed the maximum response to phenylephrine in stomach but not in aorta. Furthermore, isomeric activity ratios of the isomers of dibozane in two organs were significantly different to indicate receptor site dissimilarity. The ratios on aorta and stomach were 37 and 10, respectively. Meso-dibozane was as effective as the potent SS-dibozane. Although the stereoisomers of epinephrine did not distinguish between the receptors in the two tissues, the dose-response curves of tetrahydrozoline isomers in each tissue were markedly different. In the receptor containing membrane fractions from aorta and stomach fundus, the binding of the racemic [3H]WB-4101 was saturable with maximum receptor-related binding at 2 and 0.4 pmol/g, respectively. The dissociation constant for the blocker in the fraction from aorta and stomach was 0.8 and 0.5 nM, respectively. The ratio for the displacement of racemic [3H]WB-4101 by the stereoisomers of WB-4101 in each type of the subcellular fraction was different. The dissociation constants of both (R)- and (S)-WB-4101 obtained in the subcellular fraction were remarkably close to that observed in intact aortic strips. In the subcellular fraction from the stomach, however, the dissociation constants were higher than that observed in intact tissues. A highly complex set of [3H]WB-4101 displacement curves were obtained when the stereoisomers of dibozane were examined. In the membrane fraction from rabbit aorta, RR-dibozane and tetrahydrozoline isomers caused a concentration dependent inhibition of [3H]WB-4101 binding, the maximum receptor-related displacement by these isomers, however, was not as great as that observed with (R)- or (S)-WB-4101. The manner in which these stereoisomers interact with the functional groups of alpha adrenoreceptors must differ. In summary, data obtained with the aid of stereoisomers of adrenergic stimulants and blockers which were tested either in intact tissue or the subcellular fractions indicate that the alpha adrenoreceptors in the two tissues must differ.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume217
Issue number1
StatePublished - 1981
Externally publishedYes

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Aorta
Stomach
Stereoisomerism
Rabbits
Subcellular Fractions
Phenylephrine
Epinephrine
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
Adrenergic Antagonists
Membranes
Adrenergic Receptors
dibozane

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Alpha adrenoreceptors of rabbit aorta and stomach fundus. / Fuder, H.; Nelson, W. L.; Miller, Duane; Patil, P. N.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 217, No. 1, 1981, p. 1-9.

Research output: Contribution to journalArticle

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