Rapid inhibition of the contraction of rat tail artery by progesterone is mediated by inhibition of calcium currents.
Progesterone induced rapid relaxation of KCl-contracted tail artery helical strips from rats. The effect was dose dependent, with an IC50 (inhibitory concentration which produces 50% of the maximal response) of 8.9 microM progesterone. The actions of progesterone were not blocked by bicuculline, indicating that in this tissue the non-genomic actions of progesterone were not mediated via a gamma-aminobutyric acid (GABA)-A receptor. Fura-2 was used to measure intracellular calcium levels ([Ca(2+)](i)) in isolated vascular smooth muscle cells (VSMC). Incubation of cultured VSMC for 15 min with progesterone (10 microM) resulted in an inhibition of the KCl-induced [Ca(2+)](i )increase. The whole-cell patch-clamp technique was used to examine Ca(2+)-channel currents in the membrane of isolated VSMC. Progesterone suppressed the L-type Ca(2+)-channel currents in cells held at a potential of -40 mV. The effects of progesterone were quickly reversed by washout in all three experimental protocols suggesting that these effects on vascular tissues are non-genomic. The correlation of the effects on all these preparations, their time course and reversibility suggested that the rapid relaxation of the rat tail artery induced by progesterone is mediated at least in part by inhibition of L-type calcium channels, leading to inhibition of calcium responses in the VSMC of this tissue.
Zhang
Meili
M
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Benishin
Christina G
CG
Pang
Peter K T
PK
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003864:Depression, Chemical; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
D020746:Calcium Channels, L-Type; D018756:GABA Antagonists; D011374:Progesterone; D011189:Potassium Chloride; D002118:Calcium; D001640:Bicuculline