Investigation of the subtypes of α1‐adrenoceptor mediating contractions of rat aorta, vas deferens and spleen

• Published in: British journal of pharmacology Vol. 109; no. 1; pp. 80 - 87
• Main Authors: Aboud, R., Shafii, M., Docherty, J.R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1993; Nature Publishing
• Subjects: 5‐methyl‐urapidil; benoxathian; Biological and medical sciences; Catecholaminergic system; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; prazosin; rat aorta; rat spleen; Rat vas deferens; WB 4101; α1A‐adrenoceptors; α1B‐adrenoceptors; Rat; Rodentia; α1-Adrenergic receptor; Identification; Male genital system; Muscle contraction; Vas deferens; Vertebrata; Mammalia; Animal; Blood vessel; Aorta; Mechanism of action
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13534.x

1 The subtypes of α1‐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 pA2 values of 9.26, 9.54, 9.02 and 8.43, respectively. The irreversible antagonist chloroethylclonidine (CEC) (100 μm) failed to affect contractions to NA. 3 In rat vas deferens in the presence of nifedipine (10 μm), contractions to NA were significantly attenuated and under these conditions, CEC (100 μm) significantly reduced the maximum response to NA. 4 In rat spleen, the competitive antagonists prazosin, WB 4101 and benoxathian inhibited contractions to phenylephrine with pA2 values of 9.56, 8.85 and 7.60, respectively, and 5‐methyl‐urapidil had a KB of 6.62. CEC (100 μm) 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 pA2 values of 9.45, 9.21, 8.55 and 8.12, respectively. CEC (100 μm) 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 μm), the isometric contraction to a single electrical pulse was significantly reduced by CEC (100 μm), and by the competitive antagonists prazosin, WB 4101, benoxathian and 5‐methyl‐urapidil at concentrations of 1 nm. 7 In prostatic portions of rat vas deferens, the α1‐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 μm). 8 Contractions of rat vas deferens produced by NA (and amidephrine) are mediated predominantly by α1A‐adrenoceptors as shown by the high potency of α1A‐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 α1B‐adrenoceptors since α1A‐selective antagonists showed low potency and CEC significantly reduced the maximum contraction to phenylephrine. Contractions of rat aorta to NA are mediated by non‐α1A, non‐α1B‐adrenoceptors, due to the high potency of the α1A‐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 α1A‐selective antagonists showed high potency, suggesting that this response is mediated by non‐α1A, non‐α1B‐adrenoceptors. 10 In conclusion, at least three subtypes of functional α1‐adrenoceptors have been demonstrated in these studies.