Effect of the Ca(2+)-channel agonist Bay K 8644 on the contractile responses in human placental veins.
1. The aim of the present study was to analyse, in segments of human placental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+ channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1 microM) caused small concentration dependent contractions that were increased by a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with 75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1 microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration dependent contractile responses which were increased by Bay K 8644 (0.1 microM). Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+ accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and 30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal level that was increased by Bay K 8644 (0.1 microM). Such an increase was antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small depolarization with K+ is needed for Bay K 8644 to be able to produce consistent contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are not activated in a basal situation in placental veins; (2) the increase of 5-HT contraction by Bay K 8644 may be produced by either the capability of this amine to depolarize the membrane of smooth muscle cells and subsequent facilitation of Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT) operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.
Barrús
M T
MT
Departmento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Reviriego
J
J
Marín
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D012039:Regional Blood Flow; D012701:Serotonin / Q000494:pharmacology; D014680:Veins / Q000187:drug effects
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium