Pharmacological characterization of alpha adrenergic receptors in the young and old female rabbit urethra

M Yoshida, J Latifpour, T Nishimoto and RM Weiss

Section of Urology, Yale University School of Medicine, New Haven, Connecticut.

The pharmacological characteristics of alpha-1 and alpha-2 adrenergic receptors in young (6 month) and old (4.5-5 year) female rabbit urethra were studied using isolated muscle bath techniques. Norepinephrine, phenylephrine, clonidine, oxymetazoline and UK 14,304 produced concentration-dependent contractions in both age groups. The maximum contractile responses (Emax) to norepinephrine, phenylephrine, oxymetazoline and UK 14,304 were of similar magnitude and were significantly greater than the contractile responses to clonidine. The rank order of the ED50 values for these drugs was: oxymetazoline less than UK 14,304 much less than clonidine = norepinephrine = phenylephrine. Prazosin (10(-8) M) shifted the concentration-response curves to phenylephrine and UK 14,304 to the right, but did not shift the concentration-response curves to clonidine and oxymetazoline. Yohimbine (10(-7) M) shifted the concentration-response curves to clonidine, oxymetazoline and UK 14,304 to the right, but did not shift the concentration-response curve to phenylephrine. The ED50 values for phenylephrine and clonidine were smaller in the older than in the younger age group. There were no other age-dependent differences in the response to agonists. Pretreatment with chlorethylclonidine, which selectively alkylates the alpha-1B subtype, did not affect the Emax value of phenylephrine-induced contractions, but significantly shifted the curve to the right. The ratios of the Emax values in Ca++ free buffer to that in normal Ca++ buffer for phenylephrine, UK 14,304, clonidine, oxymetazoline and KCl were 0.30, 0.38, 0.08, 0.07 and 0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 257, Issue 3, pp. 1100-1108, 06/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics