Modulation of voltage-operated, but not receptor-operated, calcium channels in the rabbit aorta by PK 11195, an antagonist of peripheral-type benzodiazepine receptors.
We compared the effects of PK 11195, an antagonist of peripheral benzodiazepine receptors, on contractions of rabbit aorta by activation of either voltage-operated calcium channels (VOC) using BAY K 8644 (a calcium "agonist") and KCl or receptor-operated channels (ROC) using phenylephrine and B-HT 920, (alpha 1- and alpha 2-adrenoceptor agonist, respectively). In partially depolarized muscle strips, BAY K 8644 induced contractions that were noncompetitively inhibited by PK 11195 (pD'2 = 5.6 +/- 0.15). The effect of this calcium agonist was also antagonized by nitrendipine (competitively) and by yohimbine (noncompetitively), while prazosin was inactive. Contractions induced by KCl were inhibited by nitrendipine and, weakly, by PK 11195. Contractions induced by phenylephrine and B-HT 920 were inhibited competitively by prazosin and yohimbine and noncompetitively by nitrendipine, while PK 11195 was ineffective. It is concluded that PK 11195 behaves as an antagonist of VOC activated by BAY K 8644 and to a lesser extent by KCl depolarization but not of ROC coupled to alpha 1- and alpha 2-receptors.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007473:Ion Channels; D007546:Isoquinolines; D011963:Receptors, GABA-A; D010656:Phenylephrine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C024763:talipexole; D009543:Nifedipine; D002118:Calcium; C037850:PK 11195