title: Interaction of U-50,488H with calcium channel agonists and antagonists in different cardiac tissues.
abstract: 1. The present study examined the interaction of U-50,488H (specific k-agonist) with diltiazem (calcium channel antagonist) or Bay K 8644 (calcium channel agonist) on isolated left and right atria of the rat. 2. The inhibitory effects of U-50,488H on left and right atria were unaffected by the k-receptor antagonist MR-2266 (10(-7) and 5 x 10(-7) M) suggesting that they were not mediated via opioid receptors. 3. The inhibitory cardiac effects induced by U-50,488H were antagonized in presence of Bay K 8644. The negative inotropic response to the maximum concentration of U-50,488H used in presence of two concentrations of Bay K 8644 (10(-9), 3 x 10(-9) M) were 19 +/- 0.9% and 9 +/- 0.1% reductions in contractility respectively. These values were significantly (P < 0.001) lower than that obtained with the k-agonist alone (76 +/- 3.6%). Similar results were obtained for the negative chronotropism of right atria. 4. The inhibitory effect of U-50,488H was potentiating in the presence of diltiazem (5 x 10(-8) or 10(-7) M). The IC50 values for U-50,488H obtained in the left (22 +/- 2 x 10(-6) M) and right atria (610 +/- 40 x 10(-6) M) were significantly (P < 0.001) decreased in the presence of diltiazem. 5. These data demonstrate that transmembrane calcium influx may play an important role in the inhibitory cardiac effects of U-50,488H, which may be independent of k-receptor stimulation.
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001575:Benzomorphans / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors
chemical_list: D000959:Antihypertensive Agents; D001575:Benzomorphans; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004110:Diltiazem