Antagonizing Action of Chlorpromazine, Dibenamine, and Phenoxybenzamine on Potassium-Induced Contraction

Abstract

When rabbit aortic strips were incubated for 1 hour in Ringer's solution containing 10−5 M chlorpromazine, 10−4 M Dibenamine, or 10−4 M phenoxybenzamine, or 2 hours in calcium-free Ringer's solution, they failed to respond to high potassium (10–80 mM). With increasing external calcium this inhibitory action on the potassium-induced contraction decreased. Incubation in solutions containing 10−4 M phentolamine, dihydroergotamine, yohimbine, azapetine, pronethanol, dichloroisoproterenol, or MJ 1998 did not inhibit the response to potassium. The responses to angiotensin (5 × 10−7 M) were not antagonized by any of the blocking agents. It was found that the three agents blocking the potassium-induced contraction inhibited calcium-45 uptake during these contractions; however, they did not inhibit the calcium-45 uptake of unstimulated muscle. The other agents tested failed to decrease the calcium-45 influx during potassium contraction. There were no tissue electrolyte changes found after treatment of the aortas with any of the agents. The results suggest that the inhibition observed was mediated by a decrease in calcium movement rather than a decrease in potassium movement into the intracellular space.

Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia

“…Recently, Bkaily et al (1984) showed that trifluoperazine (TFP), a potent calmodulin inhibitor, blocks the slow action potential and causes excitation-contraction uncoupling in cultured chick embryonic heart cells. Cpz was reported to inhibit the potassium-induced contraction of vascular smooth muscles by restricting the voltage-dependent calcium influx through the cell membrane (Shibata & Carrier, 1967). In voltage clamp experiments on frog semitendinosis muscle, TFP and W-7 were shown to be effective in blocking the voltage-dependent calcium inward current (Johnson et al, 1982).…”

The effect of drugs on the constriction of isolated depolarized blood vessels in response to calcium or barium

“…Vascular smooth muscle ceases to respond to constrictor agents in the absence of calcium (Evans, Schild & Thesleff, 1958;Briggs & Melvin, 1961;Bohr & Goulet, 1961;Briggs, 1962;Waugh, 1962;Hinke, Wilson & Burnham, 1964;Cuthbert & Sutter, 1965;Axelsson, Johansson, Jonsson & Wahlstrom, 1966;Briggs & Shibata, 1966;Shibata & Briggs, 1966;Alexander, 1967;Burks, Whitacre & Long, 1967;Northover, 1967a;Shibata & Carrier, 1967;Hudgins & Weiss, 1968). Several of these reports also mention that calcium ions cause constriction of depolarized blood vessels.…”

“…A contractile protein can be extracted from vascular smooth muscle which resembles actomyosin from skeletal muscle in that it develops ATP-ase activity and contracts under the influence of calcium ions (Bohr, Filo & Guthe, 1962). There is evidence that extracellular calcium ions enter the vascular smooth muscle cell in response to substances which produce contraction (Briggs, 1962;Waugh, 1962;Briggs & Shibata, 1966;Shibata & Carrier, 1967). In addition to the entry of extracellular calcium, the activity of some vasoactive drugs is best explained by the release of membrane-bound intracellular calcium in the vicinity of the contractile proteins (Hinke et al, 1964;Cuthbert & Sutter, 1965Jhamandas & Nash, 1967Hudgins & Weiss, 1968).…”

Reversible and irreversible inhibition by anesthetics of the calcium-induced luminescence of aequorin.

“…Plastic laboratory ware was used throughout the experiment to avoid contamination by Cla2+ from glassware. [2] in which m is the number of the drug molecules attached to one molecule of protein to form the complex EAn and n is the number of drug molecules combined to one molecule of the complex EArn in the destruction process.…”

“…The so-called membrane-stabilizing actions of local anesthetics, general anesthetics, tranquilizers, and narcotics are frequently explained by their antagonistic action on Ca2+ (1)(2)(3)(4)(5)(6).…”