The Action of the Ionophores, X-537A and A-23187, on Smooth Muscle

Abstract

The cation ionophore X-537A in the concentration range of 10(-6) to 3 X 10(-5) M produced contractions in the rat and guinea-pig vas deferens. No contractile effect was produced in either of the vasa deferentia preparations by the ionophore A-23187 in the concentration range of 10(-7) to 5 X 10(-5) M. In contrast, X-537A had no contractile effect on the guinea-pig ileal longitudinal smooth muscle while A-23187 produced a dose and [Ca2+] dependent contraction. The contractile effect of X-537A in the vasa deferentia preparations is abolished by phenoxybenzamine or prior reserpine treatment and is therefore attributed to the release of norepinephrine. The effect of A-23187 in the intestinal smooth muslce is attributed to a direct Ca2+ transporting action since its contractile effect is unaffected by histamine, acetylcholine, or 5-hydroxytryptamine antagonists.

Relaxing and metabolic inhibitory action of X537A (Lasalocid) on the taenia of the guinea‐pig caecum.

“…Swamy et al (1975) have also reported that X537A inhibits contractile responses to agonists in the intestine.…”

“…In the vas deferens, unlike A23187, X537A released catecholamine in the absence of calcium (Thoa, Costa, Moss & Kopin, 1974;Ito, Nakazato & Ohga, 1978). Swamy et al (1975) further reported that X537A did not produce a contraction but inhibited the contractile response to muscarinic agonists in the guinea-pig ileal longitudinal smooth muscle. The inhibitory action of X537A on contractile responses to potassium was also observed in vascular smooth muscles (Watson, 1978;Bukoski, Seidel & Allen, 1979;Berner, Disalvo & Schwartz, 1980).…”

“…A23187 is well documented to cause contractions of various smooth muscles dependent upon the presence ofexternal calcium (Murray, Reed & Fay, 1975;Swamy, Ticku, Triggle & Triggle, 1975;Mandrek & Golenhofen, 1977;Ishida & Shibata, 1980), although Watson (1978) suggested that A23187 does not work solely by increasing the permeability of the cell membrane to calcium in vascular smooth muscles. Further, calcium influx inhibitors such as verapamil and D600 were able to inhibit the contractile response to A23 187 in guinea-pig gastro-intestinal smooth muscle including the taenia (Mandrek & Golenhofen, 1977) and guinea-pig vas deferens (Ishida & Shibata, 1980).…”

“…X537A has been reported to cause the release of endogenous catecholamines, resulting in contraction of vascular smooth muscles (Levy, Cohen & Insei, 1973;Haeusler, 1976;Watson, 1978) and guinea-pig vas deferens (Swamy et al 1975). In the vas deferens, unlike A23187, X537A released catecholamine in the absence of calcium (Thoa, Costa, Moss & Kopin, 1974;Ito, Nakazato & Ohga, 1978).…”

Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats

“…A23187 produces a contraction which is dependent on the external Ca2+ in smooth muscles (Ishida & Shibata, 1980) by increasing the permeability of the membrane to Ca2+ (Swamy et al, 1975). However, the contraction induced by A23187 was insensitive to verapamil and mexiletine did not induce relaxations in arteries contracted with A23187, indicating that mexiletine does not nonspecifically inhibit contractions which depend on extracellular Ca2+.…”