The effect of magnesium and calcium on the physiological properties of certain purine derivatives

Abstract

We have described previously some of the pharmacological actions of adenosine triphosphate and related compounds. The purpose of this work is to show how and to what degree Mg and Ca laffect the circulatory reactions to these purine derivatives. It has already been reported (Bielschowsky & Green, 1944) that the Mg salt of adenosine triphosphate is more toxic than.the Na salt and that free Mg++* is capable of potentiating the toxic action of this and other purine derivatives (Green & Stoner, 1944). Consequently, it was important to determine the effect of Mg on other properties of these compounds. To this end, the circulatory effects of the Na and Mg salts of these subst3nces were compared, and the action of free Mg++ on these effects observed. Since Ca antagonizes some of the pharmacological effects of Mg, its influence on these compounds was also studied. Drury & Sz8nt-Gy6rgyi (1929) have already observed the effect of free Ca++ on the response of the heart to adenylic acid and adenosine and found that there was no alteration with doses up to 5 mg. The only substances found to modify the action of these two compounds were Ba and phosphotungstic acid, the former decreasing and the latter intensifying their action on the heart. METHODSThe investigation was carried out on a series offorty-nine cats, three rabbits and one dog, anaesthetized either with nembutal or chloralose. The results obtained, with one exception which will be mentioned later, were identical with both anaesthetics. The blood pressure was recorded from the carotid artery with a mercury manometer. The intravenous injections were given into the external jugular vein or a radicle of the portal vein and washed in with physiological salt solution from a burette. In some experiments the contractions of the left ventricle were recorded with a Cushny myograph and the contractions of the right auricle by a thread attached to its apex.Intestinal volume changes were recorded with an oncometer connected to a tambour recorder and, in some experiments, a blood-press#ure compensator (Bayliss, 1908) was attached to a cannula in the iliac artery. At the beginning of the majority of the experiments in which free Mg+ + was used, both uretexs were ligated to stabilize the level of the blood Mg (Hoff, Smith & Winkler, 1939).* This term signifies that Mg+ + was injected separately.

An estimate of adenosine triphosphate release into the venous effluent from exercising human forearm muscle

“…The question arises whether ATP can be released into the circulation during exercise in sufficient quantities to affect other systems. ATP is known to have profound effects on the cardiovascular and respiratory systems when injected into the circulation (Drury & Szent-Gyorgyi, 1929;Gaddum & Holtz, 1933;Gillespie, 1934;McDowall, 1944;Bielschowsky, Green & Stoner, 1946;Emmelin & Feldberg, 1948;Davies, Gropper & Schroeder, 1951). Emmelin & Feldberg gave 200,g (364 n-mole) ATP i.v.…”

Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.

“…The confusion appears to be due, at least in part, to the fact that different regions of the heart respond to ATP in different ways (see Drury, 1936). Its chronotropic and inotropic effects are predominantly negative on isolated mammalian atria (dog: Emmelin & Feldberg, 1948;cat: Green & Stoner, 1950; Acierno, Burno, Burnstein & Di Palma, 1952;Bertelli, Bianchi & Beani, 1972; rabbit: Bielschowsky, Green & Stoner, 1946; Emmelin & Feldberg, 1948; Bertelli et al 1972;rat: Hollander & Webb, 1957;Bertelli et al 1972;Meinertz, Nawrath & Scholz, 1973), but positive on both mammalian (rabbit: Green & Stoner, 1950: Gillespie, 1934) and amphibian (Lindner & Rigler, 1931;Lichtneckert & Straub, 1949;Loewi, 1949;Marshall & Andrus, 1953;Szent Gy6rgyi, 1953; Kanda, Sekiya & Inoue, 1954;Schenberg, 1956; Versprille, 1963Versprille, , 1965Boyd & Forrester, 1968) ventricles. Not surprisingly, then, the responses to ATP of isolated whole hearts, and those produced by injection into intact animals, are complex (cats: Bielschowsky et al 1946;Emmelin & Feldberg, 1948;Green & Stoner, 1950;dogs: Emmelin & Feldberg, 1948;Angelakos & Glassman, 1961; rabbit : Sydow & Ahlquist, 1954;Buckley, Tsuboi & Zeig, 1961; guinea-pig: Rand, Stafford & Thorp, 1955;rat: Versprille & Van Duyn, 1966; man: Wayne, Goodwin & Stoner, 1949).…”

Systemic Effects of Adenosine Triphosphate

“…After a latency of some 30 seconds, the time necessary for the ATP to reach the general circulation after having passed through the tibialis anticus muscle, respiratory changes occurred, followed by strong contractions of the skeletal muscles of the limbs and the whole body of the animal. ATP is known to produce profound changes in the cardio-vascular system (Drury and Szent-Gyorgyi, 1929;Gaddum and Holtz, 1933;Gillespie-, 1934;McDowall, 1944;Bielschowsky, Green and Stoner, 1946) and the possibility was therefore envisaged that these general effects might be the outcome of circulatory events.The present paper deals with circulatory, respiratory, and other systemic effects of ATP when injected into different parts-of the circulatory system. cannulated in this case.…”