Quinine and Caffeine Effects on 45Ca Movements in Frog Sartorius Muscle

Abstract

1 mM caffeine, which produces only twitch potentiation and not contracture in frog sartorius muscle, increases both the uptake and release of ~Ca in this muscle by about 50 %, thus acting like higher, contracture-producing concentrations but less intensely. Quinine increases the rate of release of ~Ca from frog sartorius but not from the Achilles tendon. The thresholds for the quinine effect on 4~Ca release and contracture tension are about 0.1 and 0.5 mM, respectively, at pH 7.1. Quinine (2 mM) also doubles the uptake of ~Ca by normally polarized muscle. However, there are variable effects of quinine upon ~Ca uptake in potassium-depolarized muscle. Quinine (2 raM), increases the Ca, Na, and water content of muscle while decreasing the K content. Both caffeine (1 raM) and quinine (2 mM) act to release ~Ca from muscles that have been washed in Ringer's solution from which Ca was omitted and to which EDTA (5 inM) was added. These results, correlated with those of others, indicate that a basic effect of caffeine and quinine on muscle is to directly release activator Ca ~+ from the sarcoplasmic reticulum in proportion to the drug concentration. The drugs may also enhance the depolarization-induced Ca release caused by extra K + or an action potential. In respect to the myoplasmic Ca 2+ released by direct action of the drugs, a relatively high concentration is required to activate even only threshold contracture, but a much lower concentration, added to that released during excitation-contraction coupling, is associated with the condition causing considerable twitch potentiation.Caffeine and quinine affect frog skeletal muscle similarly in some respects. In low concentrations (caffeine, 1 mM; quinine, 0.1 raM) they increase the tension output of the twitch; i.e., they are twitch potentiators (for review, see , whereas in somewhat higher concentrations they not only potentiate the twitch but also engender contracture, though with considerable variability (caffeine: Axelsson

Effects of sulphydryl inhibitors on frog sartorius muscle: N‐ethylmaleimide

“…The kinetics of rigour development by NEM and its effect on 45Ca efflux were similar, suggesting a relationship between the two effects. In these experiments, NEM was added to the muscle bath during a period of time when "5Ca is assumed to be emerging primarily from the sarcoplasmic reticulum (Bianchi, 1961 ;Isaacson & Sandow, 1967). If this assumption is valid, then a sustained increase in 45Ca efflux from the muscle reflects an increase in the amount of free intracellular calcium released from the sarcoplasmic reticulum.…”

“…Effects on "Ca efflux An increase in rate of "Ca efflux from skeletal muscle is produced by the rigourproducing agents caffeine (Isaacson & Sandow, 1967), quinine (Isaacson & 1967; Isaacson, Yamaji & Sandow, 1970) and iodoacetic acid (Bianchi, 1963), and in each case it is thought that the calcium efflux derives primarily from the sarcoplasmic reticulum. In the present experiments, we found that rigour-producing concentrations of NEM also increase the rate of "Ca efflux.…”

The Permeability of Bull Spermatozoa to Water, Polyhydric Alcohols and Univalent Anions and the Effects of the Anions Upon the Kinetic Activity of Spermatozoa and Sperm Models

“…Caffeine also inhibits the phosphodiesterase which converts cyclic AMP into 5-AMP (Berthet, Sutherland & Rail, 1957;Sutherland & Rail, 1958) which may possibly be beneficial for motility. Furthermore, caffeine may, as in muscle (Bianchi, 1963;Isaacson & Sandow, 1967), release Ca+ + from bound sites in the spermatozoa and inactiv¬ ate a sperm-relaxing factor (cf. Bishop, 1962) and/or activate the ATPases of the flagellar fibres which are Ca++ dependent (cf.…”

Biphasic effect of methylxanthines on acetylcholine release from electrically‐stimulated brain slices

“…They also affect intracellular calcium mobilization (Isaacson & Sandow, 1967;Johnson & Inesi, 1969) and inhibit the release of adenosine from cortical slices . Since the inhibitory effect of caffeine was not modified by pretreating the rats with ax-methyl-p-tyrosine in a dose which reduces brain catecholamine levels (Berkowitz et al, 1970), the involvement of a noradrenergic mechanism can be excluded.…”