The spasmogenic action of oxytocin in the rat uterus – comparison with other agonists

Abstract

1 A low concentration (0.2 nm) 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 nm). 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 μm). 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 μm. 3 (−)−cis Diltiazem was less potent than (+)-cis diltiazem as an inhibitor of calcium (Ca²⁺)-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 Ca²⁺-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 nm) 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 nm) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)-cis diltiazem (10 μm), oxytocin (0.2, 2 and 20 nm) produced graded tonic spasm without spike activity. 6 Oxytocin (0.2 nm) produced a small increase in ⁴⁵Ca²⁺ influx into myometrium as assessed by the ‘lanthanum method’. Higher concentrations of oxytocin (2 and 20 nm) did not increase ⁴⁵Ca²⁺ influx. 7 It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca²⁺ influx via voltage-dependent Ca²⁺ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca²⁺ influx. All of the spasmogenic response to KCl can be explained by Ca²⁺ influx through voltage-dependent Ca²⁺ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.