An examination of the putative σ-receptor in the mouse isolated vas deferens

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Abstract
1 The effects of several ligands which interact with the σ-binding site were studied on the electrically-evoked (0.1 Hz) neurogenic twitch contractions of the mouse isolated vas deferens. 2 (+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) (10−8–10−5m), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10−6m), idazoxan (10−6m), cocaine (10−6m) or tyramine (10−4–3 × 10−4m), but was abolished by the dopamine D2-antagonist, sulpiride (10−6m). Therefore, in order to study the potentiating actions of σ ligands, sulpiride (10−6m) was used to prevent any inhibitory actions mediated via dopamine D2-receptors. 3 In the presence of sulpiride (10−6m), haloperidol (10−6–10−5m), (+)-3-PPP (10−6−3 × 10−4m) and (+)-N-allyl-N-normetazocine ((+)-SKF 10,047) (10−5–10−4m) each reversibly potentiated the neurogenic twitch contractions in a concentration-dependent manner. The rank order of potency was haloperidol > (+)-3-PPP > (+)-SKF 10,047. 4 The stereoisomers of 3-PPP displayed stereoselectivity with (+)-3-PPP being more potent than (−)-3-PPP. 5 At a concentration that did not potentiate the twitch contractions, (3 × 10−7m), haloperidol did not antagonize the potentiating action of (+)-3-PPP (3 × 10−5m). 6 1,3-Di-O-tolyguanidine (DTG) (10−8–10−5m) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)-3-PPP (10−5−3 × 10−5m). 7 It is concluded that σ-ligands potentiate neurogenic twitch contractions of the mouse isolated vas deferens via a site that is different from the central σ-binding site.