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An examination of the putative σ‐receptor in the mouse isolated vas deferens
Author(s) -
Kennedy Charles,
Henderson Graeme
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12614.x
Subject(s) - vas deferens , sulpiride , haloperidol , idazoxan , chemistry , dopamine , dopamine receptor , medicine , endocrinology , antagonist , pharmacology , receptor , biology , prazosin , biochemistry
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 −5 m ), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10 −6 m ), idazoxan (10 −6 m ), cocaine (10 −6 m ) or tyramine (10 −4 –3 × 10 −4 m ), but was abolished by the dopamine D 2 ‐antagonist, sulpiride (10 −6 m ). Therefore, in order to study the potentiating actions of σ ligands, sulpiride (10 −6 m ) was used to prevent any inhibitory actions mediated via dopamine D 2 ‐receptors. 3 In the presence of sulpiride (10 −6 m ), haloperidol (10 −6 –10 −5 m ), (+)‐3‐PPP (10 −6 −3 × 10 −4 m ) and (+)‐N‐allyl‐N‐normetazocine ((+)‐SKF 10,047) (10 −5 –10 −4 m ) 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 −7 m ), haloperidol did not antagonize the potentiating action of (+)‐3‐PPP (3 × 10 −5 m ). 6 1,3‐Di‐ O ‐tolyguanidine (DTG) (10 −8 –10 −5 m ) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)‐3‐PPP (10 −5 −3 × 10 −5 m ). 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.