The lack of a role for potassium channel opening in the action of relaxin in the rat isolated uterus; a comparison with levcromakalim and salbutamol.
1. The effects of relaxin in vitro in the isolated uterus from the non-pregnant rat were compared with those of levcromakalim and salbutamol in tissue bath, 42K+ -efflux and electrophysiological studies, to determine whether relaxin exhibits the characteristics of an opener of KATP-channels. 2. In uterus exposed to oxytocin (0.2 nM), tetraethylammonium (TEA, 10 mM) and glibenclamide (10 microM) produced large rightward shifts of the log10 concentration-effect curve to levcromakalim (125 fold and 118 fold, respectively). TEA (10 mM) caused only small rightward shifts of the log10 concentration-effect curves to salbutamol and relaxin (5.2 fold and 7.5 fold respectively). Glibenclamide did not antagonize salbutamol or relaxin. 3. Levromakalim (0.2 and 2 microM) suppressed the spasm evoked by low ( < or = 40 mM) but not high ( > 40 mM) concentrations of KCl. Salbutamol (1.5 nM) inhibited the spasm evoked by low concentrations of KCl ( < or = 40 mM). Salbutamol (15 nM) and relaxin (3 and 30 nM) inhibited the spasm evoked by low and high concentrations of KCl (10-80 mM). 4. Relaxin (0.12 microM) did not produce an increase in 42K+-efflux from longitudinal segments of rat myometrium. Exposure of tissues to relaxin (0.12 microM), in the presence of diltiazem (1 microM) plus KCl (20 mM), resulted in a small increase in 42K+-efflux of short duration. 5. Electrophysiological recording showed that the phasic spasms of the uterus exposed to oxytocin (0.2 nM) were accompanied by bursts of spiking activity superimposed upon a plateau potential. Inhibition of the mechanical activity of the uterus by levcromakalim (2 and 10 microM), salbutamol (30 nM) or relaxin (0.18 microM) was accompanied by a reduction in the duration of the plateau potential and the number of spikes without membrane hyperpolarization. 6. Unlike levcromakalim, relaxin did not selectively inhibit the spasm evoked by low concentrations of KCl and was not markedly antagonized by TEA or glibenclamide. Under conditions where a cromakalim-induced increase of the 42K+-efflux rate has been demonstrated, relaxin had only a very small effect. In isolated uterus from the rat, in contrast to observations in vivo, relaxin did not exhibit the characteristics of an opener of KATP-channels suggesting that another mechanism accounts for its inhibitory action.
Hughes
S J
SJ
School of Biological Sciences, University of Manchester.
Hollingsworth
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004594:Electrophysiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D010121:Oxytocin; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000494:pharmacology* / Q000502:physiology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D010121:Oxytocin; D011189:Potassium Chloride; D012065:Relaxin; D000420:Albuterol; D005905:Glyburide