Fenoterol and salbutamol actions on guinea-pig myometrium: Effects of ovarian steroids

Mammen, George J.; Handberg, Gwynneth M.; Story, Margot E; Pennefather, Jocelyn N.

doi:10.1016/0014-2999(87)90537-1

Cited by 2 publications

(1 citation statement)

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“…Oestrogen treatment is also accompanied by decreased levels of myometrial Gs (Roberts et al 1989). In addition, pro¬ gesterone uncouples a2-adrenoceptors from adenylate cyclase inhibition in the rabbit uterus, while in the guinea-pig this treatment increases myometrial sensi¬ tivity to ß-adrenoceptor-mediated relaxation; changes which appear independent of receptor number, agonist binding affinity, adenylate cyclase levels and ATP concentration (Mammen, Handberg, Story & Pennefather, 1987;Roberts et al 1989). Furthermore, in ovine uterus both oestrogen and progesterone increase levels of a membrane protein demonstrating characteristics of a G-protein (Flint, 1988).…”

Section: Introductionmentioning

confidence: 96%

Influence of pregnancy on G-protein coupling to adenylate cyclase activation in guinea-pig myometrium

Arkinstall

Jones²

1990

Journal of Endocrinology

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The regulatory factors controlling uterine activity during pregnancy remain unclear in many species. Since myometrial relaxants raise intracellular cyclic AMP, modulation of signalling pathways coupling cell-surface receptors to adenylate cyclase activation could be an important site for control. To assess the functional activity of the stimulatory GTP-binding protein Gs we have measured adenylate cyclase activation by GTP, its non-hydrolysable analogue guanosine 5'-(beta-gamma-imido)triphosphate (Gpp(NH)p), fluoride, forskolin and manganese in a 50,000 g membrane fraction prepared from the myometrium of non-pregnant, mid-pregnant (30-32 days) and late-pregnant (62-66 days) guinea-pigs (full term 67 +/- 2 days). While forskolin- and manganese-dependent enzyme activation was unaltered by pregnancy, maximal stimulation by Gpp(NH)p and fluoride was enhanced by up to 200%. Recovery of adenylate cyclase activity in the 50,000 g fraction was essentially constant at 20-24% of the total activity throughout pregnancy, and thus cannot explain the increases observed. Since guanine nucleotides and fluoride stimulate adenylate cyclase through activating Gs, and forskolin and manganese act at the level of the catalytic unit, these data are consistent with a pregnancy-related increase in Gs functional coupling while adenylate cyclase activity is unaltered. These observations suggest a physiological regulation of myometrial Gs activity during pregnancy which could facilitate hormonal stimulation of adenylate cyclase and contribute to uterine quiescence by increasing uterine sensitivity to relaxants.

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Section: Introductionmentioning

confidence: 96%