title: Investigation of the subtypes of alpha 1-adrenoceptor mediating contractions of rat aorta, vas deferens and spleen.
abstract: 1. The subtypes of alpha 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 pA2 values of 9.26, 9.54, 9.02 and 8.43, respectively. The irreversible antagonist chloroethylclonidine (CEC) (100 microM) failed to affect contractions to NA. 3. In rat vas deferens in the presence of nifedipine (10 microM), contractions to NA were significantly attenuated and under these conditions, CEC (100 microM) 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 microM) 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 microM) 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 microM), the isometric contraction to a single electrical pulse was significantly reduced by CEC (100 microM), 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 alpha l-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 microM).8. Contractions of rat vas deferens produced by NA (and amidephrine) are mediated predominantly by alpha lA-adrenoceptors as shown by the high potency of alpha lA-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 alpha lB-adrenoceptors since alpha 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-alpha lA, non-alpha lB-adrenoceptors, due to the high potency of the aMA-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 alpha 1 A-selective antagonists showed high potency, suggesting that this response is mediated by non-alpha lA, non-alpha 1B-adrenoceptors.10. In conclusion, at least three subtypes of functional alpha 1-adrenoceptors have been demonstrated in these studies.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Aboud
authors.forename: M
authors.initials: M
authors.lastname: Shafii
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004822:Epididymis / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009638:Norepinephrine