The expression of functional postsynaptic α 2 ‐adrenoceptors in the corpus cavernosum smooth muscle

1 The purpose of this study was to determine if corpus cavernosum smooth muscle expresses functional postsynaptic α 2 ‐adrenoceptors (AR). 2 The α 2 ‐adrenoceptor agonist UK 14,304 elicited concentration‐dependent contractions in rabbit corpus cavernosum smooth muscle (CCSM). The half‐maximal response occurred at 0.32±0.03 μ M and the maximum contraction at 10 μ M UK 14,304. 3 Pretreatment of CCSM strips with selective α 2 ‐adrenoceptor antagonists, rauwolscine and RS‐15385, produced rightward shifts in the dose‐response curves to UK 14,304 (pA 2 values 7.1 and 8.5, respectively). In contrast, these antagonists did not alter contraction induced by the α 1 ‐adrenoceptor agonist phenylephrine (PE) or oxymetazoline. UK 14,304‐induced contractions were also inhibited by prazosin (pA 2 =9.08). 4 UK 14,304‐induced contractions, unlike those to PE, were highly dependent on the presence of extracellular Ca 2+ . 5 [ 3 H]‐rauwolscine bound to CCSM membranes with high affinity ( K d =1.5 n M ). [ 3 H]‐rauwolscine binding was displaced by unlabelled rauwolscine, RS‐15385, UK 14,304 and prazosin, but not by PE. 6 UK 14,304 inhibited forskolin and prostaglandin E 1 (PGE 1 )‐induced increases in intracellular cyclic AMP concentration in primary cultures of rabbit CCSM cells. 7 These results demonstrate that CCSM expresses G i ‐coupled postsynaptic α 2 ‐adrenoceptors, and activation of these receptors causes contraction of trabecular smooth muscle.British Journal of Pharmacology (1998) 123 , 1237–1245; doi: 10.1038/sj.bjp.0701739