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Investigation of the subtypes of α 1 ‐adrenoceptor mediating contractions of rat vas deferens
Author(s) -
Honner Valerie,
Docherty J R
Publication year - 1999
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 - 10.1038/sj.bjp.0702913
Subject(s) - vas deferens , prazosin , endocrinology , medicine , phentolamine , tonic (physiology) , methoxamine , phenylephrine , chemistry , spiperone , rauwolscine , contraction (grammar) , yohimbine , stimulation , agonist , receptor , antagonist , biology , blood pressure
The subtypes of α 1 ‐adrenoceptor mediating contractions of rat vas deferens to endogenous and exogenous noradrenaline and to the exogenous agonists methoxamine, phenylephrine and A61603 have been examined. The effects of antagonists on the shape of concentration‐response curves, both tonic and phasic, to the four agonists were analysed. Prazosin produced parallel shifts in all cases. Particularly for RS 17053 against noradrenaline, there was some evidence for a resistant component of the agonist response. High concentrations of RS 17053 (1–10 μ M ) virtually abolished tonic contractions but phasic contractions were resistant. A series of nine antagonists (the above and WB4101, benoxathian, phentolamine, BMY 7378, HV 723, spiperone) were investigated against contractions to noradrenaline. The correlation with the potency of the series of α 1 ‐adrenoceptor antagonists against contractions to noradrenaline was significant only for the α 1A ‐adrenoceptor ligand binding site ( r =0.88, n =9, P <0.01). In epididymal portions (nifedipine 10 μ M ), the isometric contraction to a single electrical pulse is α 1 ‐adrenoceptor mediated. The correlation with ligand binding sites for 11 antagonists (the above plus ARC 239 and (+)‐niguldipine) was significant only for the α 1D ‐adrenoceptor subtype ( r =0.65, n =11, P <0.05). In conclusion, tonic contractions of rat vas deferens produced by exogenous agonists are mediated predominantly by α 1A ‐adrenoceptors, although a second subtype of receptor may additionally be involved in phasic contractions. Nerve‐stimulation evoked α 1 ‐adrenoceptor mediated contractions seem to predominantly involve non‐α 1A ‐adrenoceptors, and the receptor involved resembles the α 1D ‐receptor.British Journal of Pharmacology (1999) 128 , 1323–1331; doi: 10.1038/sj.bjp.0702913