title: Changes in the mechanisms involved in uterine contractions during pregnancy in guinea-pigs.
abstract: 1. The mechanisms involved in contraction in guinea-pig myometrium were compared at mid- and late pregnancy. Tension was recorded simultaneously with either membrane potential or cytoplasmic calcium ([Ca2+]i) in strips exposed briefly to prostaglandin F2alpha (PGF). 2. PGF-induced increases in tension were underpinned by action potentials followed by sustained depolarization and biphasic increases in [Ca2+]i at mid- (peak, 879 +/- 199 nM; sustained, 298 +/- 35 nM, n = 11) and late pregnancy (peak, 989 +/- 302 nM; sustained 178 +/- 33 nM, n = 8). 3. At mid- and late pregnancy, nifedipine (10-6 M) reduced (a) the PGF-induced increase in tension to 84 and 35 %, (b) the level attained during the depolarization by 2 and 12 mV and (c) the peak rise in [Ca2+]i to 42 and 17 %. The sustained rises in [Ca2+]i were resistant to nifedipine. 4. In Ca2+-free solution (containing 1 mM EGTA), PGF elicited an increase in tension that was 26 % of that in 2.5 mM Ca2+ and an increase in [Ca2+]i (24 % of the sustained level) at mid-pregnancy but no increase in tension or [Ca2+]i at term. 5. At both stages of pregnancy, PGF decreased the level of [Ca2+]i required to elicit increases in tension comparable to those evoked by high K+o. The slope of the tension-[Ca2+]i curves were steeper in mid- than in late pregnancy. 6. In conclusion, at mid-pregnancy, the contractile response of the guinea-pig myometrium to PGF involves Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCCs) and by receptor-operated mechanisms, release of Ca2+ from intracellular stores, and an increase in the sensitivity of the contractile apparatus to Ca2+. At term the situation is different: a modest increase in the sensitivity of the contractile apparatus to Ca2+ persists and there is a major reliance on Ca2+ influx through VOCCs.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: H A
authors.initials: HA
authors.lastname: Coleman
authors.forename: J D
authors.initials: JD
authors.lastname: Hart
authors.forename: M A
authors.initials: MA
authors.lastname: Tonta
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011460:Prostaglandins F / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011460:Prostaglandins F; D009543:Nifedipine; D002118:Calcium