Calcium and calmodulin antagonists binding to calmodulin and relaxation of coronary segments
Johnson, J.D.; Fugman, D.A.
Journal of Pharmacology and Experimental Therapeutics 226(2): 330-334
1983
ISSN/ISBN: 0022-3565 PMID: 6875846 Document Number: 218458
Ca2+ antagonist drugs (also known as Ca2+ channel blockers) and the calmodulin antagonists trifluoperazine (TFP) and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were capable of half-maximally relaxing porcine coronary segments at 1.5 .times. 10-10 M for felodipine, 6.5 .times. 10-8 M for verapamil, 2.6 .times. 10-7 M for diltiazem, 7 .times. 10-7 M for prenylamine, 7 .times. 10-6 M for TFP and 45 .times. 10-6 M for W-7. Their correspondent binding to calmodulin was half-maximal at 2.8 .times. 10-6, 30 .times. 10-6, 80 .times. 10-6, 5 .times. 10-7, 5.0 .times. 10-6 and 11 .times. 10-6 M, respectively. Only prenylamine, TFP and W-7 were capable of relaxing coronaries over the same concentration range in which they bind to calmodulin. The relaxations produced by these calmodulin antagonists and prenylamine could not be overcome by contractile agonists which release Ca2+ from internal stores (histamine and serotonin), whereas the relaxations produced by felodipine, verapamil and diltiazem were readily reversed by either of these agonists. This is consistent with TFP and W-7 and to some degree prenylamine-inducing vasodilation by calmodulin antagonism and with felodipine, verapamil and diltiazem vasodilating through Ca2+ antagonism of Ca2+ channels at the level of the cell membrane.