ALPHA(1A)-ADRENOCEPTOR SUBTYPE MEDIATES CONTRACTION OF THE RAT URETHRA

1 The alpha(1)-adrenoceptor-mediated responses of the rat urethra to phenylephrine have been examined in vitro. Phenylephrine caused concentration-dependent contractions of the isolated urethra which were antagonized by WB4101 (3-30 nM) and prazosin (10-100 nM) but not idazoxan (1.5 mu M). Schild plot analysis of the antagonism by prazosin and WB4101 yielded straight lines with slopes not significantly different from unity. The pA(2) value of 9.0 for WB4101 was significantly greater than the value previously obtained at the alpha(1B)-adrenoceptor of the rat spleen. 2 5-Methylurapidil (30 nM) and abanoquil (1 nM) caused dextral shifts of concentration-response curves yielding pK(B) values of 8.3 and 9.4 respectively. Maximal responses to phenylephrine were also reduced by this concentration of abanoquil. 3 Preincubation with chloroethylclonidine (25 mu M for 40 min) failed to alter responses, but removing extracellular calcium or the presence of nifedipine (1 mu M) almost abolished contractions to phenylephrine. 4 These results indicate that the responses of the rat urethra to phenylephrine are mediated via the alpha(1A)-adrenoceptor subtype and are dependent on the influx of extracellular calcium.