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Characterization of angiotensin receptors in vascular and intestinal smooth muscles
Abstract:
1. A series of analogues of angiotensin II (AT(II)) has been used in the present experiments to characterize receptors for AT(II) in intestinal (rat stomach strip, rat colon) and vascular (rabbit aorta) smooth muscles. Two types of compounds have been chosen: (a) agonists with reduced potency, in which 4-Tyr, 6-His or 7-Pro had been substituted with L-Ala or with Gly and 1-amino-cyclopentane carboxylic acid (Acpc) and (b) competitive antagonists (8-Gly-AT(II), 8-Leu-AT(II)).2. Replacement of 4-Tyr, 6-His and 7-Pro with L-Ala decreases the potency, but does not influence the maximum effect of the analogue, while substitution of the same residue with Gly and Acpc reduces both potency and maximum effect.3. Compounds showing full size maximum responses were chosen to establish the following order of potency on the three preparations: AT(II)>4-Phe-AT(II)>7-Ala-AT(II)>6-Ala-AT(II)>4-Ala-AT(II).4. The four derivatives of AT(II) were completely inactive on tissues desensitized with AT(II). The responses to 5-hydroxytryptamine, acetylcholine and noradrenaline were not significantly modified, except for the rat colon.5. pA(2) values for the two competitive antagonists against AT(II) and 4-Phe-AT(II) were estimated in the three preparations by the use of the cascade superfusion technique. For comparison, pA(2) values were also estimated in rat stomach strips and rabbit aortas suspended in a normal organ bath, according to the method of Schild (1947). The similarities of the pA(2) values obtained in two series of experiments indicate that (a) the cascade superfusion technique is suitable for this type of study and (b) the receptor for AT(II) in the three tissues may be the same.6. It is suggested that receptors for AT(II) in intestinal and vascular smooth muscles may be the same, because (a) the order of potency of various agonists follows the same pattern, (b) the agonists are inactive on tissues desensitized with AT(II), (c) pA(2) values for competitive antagonists are similar in the three preparations.