Ž . European Journal of Pharmacology 319 1997 57–64 Cromakalim blocks the purinergic response evoked in rat vas deferens by single-pulse electrical stimulation Enzo Grana ) , Cinzia Boselli, Linda Bianchi Istituto di Farmacologia, Facolta di Farmacia, UniÕersita di PaÕia, Viale Taramelli 14, 27100 PaÕia, Italy ` ` Received 14 March 1996; revised 14 October 1996; accepted 15 October 1996 Abstract The present study was carried out to look at the influence of the K q channel opener cromakalim, compared with suramin and prazosin, on the contractile response evoked by single-pulse field stimulation and exogenous agonists in epididymal and prostatic portions of rat vas deferens. In the epididymal portion suramin abolished the first phase of the response to single shock, prazosin deeply affected the second phase and a combination of both antagonists almost completely abolished both phases. Cromakalim was able to inhibit in a Ž . concentration-dependent manner the first purinergic phase pD s5.90 "0.11 , leaving practically unaffected the second, adrenergic 2 phase. This inhibitory effect of cromakalim on the electrically evoked response was counteracted by glibenclamide. Cromakalim and prazosin, but not suramin, affected the response to exogenous noradrenaline. Suramin but not cromakalim was able to antagonize responses to a ,b-methylene-ATP. In the prostatic portion because of a less clear discrimination between adrenergic and purinergic phases of the electrically evoked response, the picture was less clear although the trend was identical. Cromakalim was not able to antagonize the response to ATP. It is concluded that in rat vas deferens cromakalim inhibits purinergic transmission by acting prejunctionally. Keywords: Vas deferens, rat; Purinergic transmission; Noradrenergic transmission; Cromakalim; Prazosin; Suramin; Glibenclamide 1. Introduction Cromakalim belongs to the group of drugs which are classified pharmacodynamically as potassium channel openers. Although the effects of these compounds in Ž smooth muscles have been extensively studied Cook and . Quast, 1990 , very little is known about their effects on autonomic nerve terminals. Inhibitory effects exhibited by cromakalim on the vascular responses to spinal cord stimu- lation have been reported to be exerted pre- rather than Ž . postjunctionally Richer et al., 1990 , but a study of nora- drenergic transmission in rat isolated mesenteric artery has provided no evidence of a prejunctional inhibitory effect of Ž cromakalim on transmitter noradrenaline release Fabiani . Ž . and Story, 1994 . Recently Docherty and Brady 1995 have found that the K q channel blocker apamin does not affect electrically induced contractions in the prostatic portion of rat vas deferens. Evidence has accumulated to ) Ž . Ž . Corresponding author. Tel.: 39-382 507-395; Fax: 39-382 507-405. suggest that cromakalim inhibits cholinergic neuro-effector Ž . transmission in guinea-pig trachea Burka et al., 1991 and Ž . ileum Zini et al., 1991 . Furthermore, it has been reported that cromakalim modulates non-adrenergic non-cholinergic Ž neurotransmission in guinea-pig airways in vivo Ichinose . and Barnes, 1990 and in guinea-pig tracheal smooth mus- Ž . cle Burka et al., 1991 . The present study was carried out to investigate possi- Ž. ble effects of cromakalim on transmitter s released from Ž adrenergic nerves such as noradrenaline and ATP Burns- tock, 1981; Hirst and Edwards, 1989; Starke et al., 1989; . Stjarne, 1989 . This possibility has been examined by ¨ studying the action of cromakalim on electrically induced contractions of the epididymal and prostatic portion of the rat isolated vas deferens. Research has been extended to study the action of suramin and prazosin on the biphasic response induced by a single shock and to investigate the effects of these antagonists and cromakalim on the contrac- tions produced by exogenous noradrenaline and a ,b-meth- ylene-ATP or ATP. 0014-2999r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved Ž . PII S0014-2999 96 00828-X