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The spasmogenic action of oxytocin in the rat uterus – comparison with other agonists
Author(s) -
Edwards Diane,
Good Diana M.,
Granger Susan E.,
Hollingsworth M.,
Robson Alison,
Small R.C.,
Weston A.H.
Publication year - 1986
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.1476-5381.1986.tb16264.x
Subject(s) - oxytocin , tonic (physiology) , acetylcholine , diltiazem , chemistry , endocrinology , medicine , bradykinin , sucrose gap , veratridine , pharmacology , depolarization , calcium , receptor , sodium , organic chemistry , sodium channel
1 A low concentration (0.2 n m ) of oxytocin induced phasic tension development in the isolated uterus of the day‐22 pregnant rat. Tonic spasm was also induced by higher concentrations of oxytocin (2 and 20 n m ). Spasmogenic responses to bradykinin and potassium chloride (KCl) also contained phasic and tonic components while acetylcholine induced tonic spasm only. 2 The phasic component of the responses to oxytocin and to bradykinin and both components of the response to KCl were inhibited by (+)‐ cis diltiazem (0.1 and 1 μ m ). The tonic component of the responses to oxytocin and to bradykinin and the responses to acetylcholine were only reduced by (+)‐ cis diltiazem at concentrations >10 μ m . 3 (−)− cis Diltiazem was less potent than (+)‐ cis diltiazem as an inhibitor of calcium (Ca 2+ )‐induced spasm in a depolarizing medium and of the phasic spasms induced by oxytocin. The two isomers were of similar potency as inhibitors of oxytocin‐induced tonic spasm. 4 Spasmogenic responses to oxytocin, bradykinin, acetylcholine and KCl were decreased when uteri were bathed in media which were Ca 2+ ‐free or of low Na + content. However, there was no correlation between the rank order of sensitivity of the four spasmogens to the changed media and to their inhibition by (+)‐ cis diltiazem. 5 Oxytocin (0.2 n m ) increased the frequency, duration and amplitude of spike activity, measured by extracellular electrical recording, in parallel with enhancement of phasic tension development. With higher concentrations of oxytocin (2 and 20 n m ) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)‐ cis diltiazem (10 μ m ), oxytocin (0.2, 2 and 20 n m ) produced graded tonic spasm without spike activity. 6 Oxytocin (0.2 n m ) produced a small increase in 45 Ca 2+ influx into myometrium as assessed by the ‘lanthanum method’. Higher concentrations of oxytocin (2 and 20 n m ) did not increase 45 Ca 2+ influx. 7 It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca 2+ influx via voltage‐dependent Ca 2+ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca 2+ influx. All of the spasmogenic response to KCl can be explained by Ca 2+ influx through voltage‐dependent Ca 2+ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.