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Investigation of the subtypes of α 1 ‐adrenoceptor mediating contractions of rat aorta, vas deferens and spleen
Author(s) -
Aboud R.,
Shafii M.,
Docherty J.R.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13534.x
Subject(s) - vas deferens , prazosin , phenylephrine , endocrinology , medicine , contraction (grammar) , nifedipine , chemistry , urapidil , muscle contraction , antagonist , calcium , receptor , blood pressure , heart rate
1 The subtypes of α 1 ‐adrenoceptor mediating contractions to exogenous noradrenaline (NA) or phenylephrine in rat vas deferens, spleen and aorta, and mediating contractions to endogenous NA in rat vas deferens have been examined. 2 In rat vas deferens, the competitive antagonists prazosin, WB 4101, benoxathian and 5‐methyl‐urapidil inhibited contractions to NA with pA 2 values of 9.26, 9.54, 9.02 and 8.43, respectively. The irreversible antagonist chloroethylclonidine (CEC) (100 μ m ) failed to affect contractions to NA. 3 In rat vas deferens in the presence of nifedipine (10 μ m ), contractions to NA were significantly attenuated and under these conditions, CEC (100 μ m ) significantly reduced the maximum response to NA. 4 In rat spleen, the competitive antagonists prazosin, WB 4101 and benoxathian inhibited contractions to phenylephrine with pA 2 values of 9.56, 8.85 and 7.60, respectively, and 5‐methyl‐urapidil had a K B of 6.62. CEC (100 μ m ) significantly reduced the maximum contraction to phenylephrine. 5 In rat aorta, the competitive antagonists, prazosin, WB 4101, benoxathian and 5‐methyl‐urapidil inhibited contractions to NA with pA 2 values of 9.45, 9.21, 8.55 and 8.12, respectively. CEC (100 μ m ) produced an approximately parallel shift in the potency of NA, without significantly reducing the maximum response. 6 In epididymal portions of rat vas deferens in the presence of nifedipine (10 μ m ), the isometric contraction to a single electrical pulse was significantly reduced by CEC (100 μ m ), and by the competitive antagonists prazosin, WB 4101, benoxathian and 5‐methyl‐urapidil at concentrations of 1 n m . 7 In prostatic portions of rat vas deferens, the α 1 ‐adrenoceptor agonist, amidephrine, produced concentration‐dependent increases in the isometric contraction to a single electrical stimulus and the maximum increase in the evoked response produced by amidephrine was unaffected by CEC (100 μ m ). 8 Contractions of rat vas deferens produced by NA (and amidephrine) are mediated predominantly by α 1A ‐adrenoceptors as shown by the high potency of α 1A ‐adrenoceptor selective antagonists and the lack of effect of CEC. A small CEC‐sensitive response, particularly in epididymal portions, was revealed in the presence of nifedipine. Contractions of rat spleen are mediated by α 1B ‐adrenoceptors since α 1A ‐selective antagonists showed low potency and CEC significantly reduced the maximum contraction to phenylephrine. Contractions of rat aorta to NA are mediated by non‐α 1A , non‐α 1B ‐adrenoceptors, due to the high potency of the α 1A ‐selective antagonists and sensitivity to CEC. 9 The noradrenergic contraction of epididymal portions of rat vas deferens in the presence of nifedipine is CEC‐sensitive, but the α 1A ‐selective antagonists showed high potency, suggesting that this response is mediated by non‐α 1A , non‐α 1B ‐adrenoceptors. 10 In conclusion, at least three subtypes of functional α 1 ‐adrenoceptors have been demonstrated in these studies.