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

Abstract

SUMMARY1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'-cyclic nucleotides have been made at various times during the ATP-induced response.2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superseded by a more slowly developing and longer-lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase.3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose-related. The duration of the action potential (DLL my) 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5'-cyclic nucleotides. The time courses of the changes in adenosine 3',5'-cyclic monophosphate (3',5'-cyclic AMP) and guanosine 3',5'-cyclic monophosphate (3',5'-cyclic GMP) are complex, but the accompanying change in isometric twitch tension is paralleled closely by corresponding changes in the ratio 3',5'-cyclic AMP: 3',5'-cyclic GMP.5. It is concluded that ATP exerts a dual effect on the ventricle and that the contractile response is regulated by changes in the metabolism of 3',5'-cyclic nucleo-0022-3751/80/8820-0252 $07.50

Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit

“…Recently, the results of a series of studies on frog ventricle by Flitney and co-workers demonstrated a remarkably precise correlation between changes in contractility and associated alterations in the levels of both cyclic AMP and cyclic GMP in response to different cardioactive agents (Singh, et al, 1978;Flitney, et al, 1979;Flitney & Singh, 1980;Singh & Flitney, 1981). In their studies Flitney and colleagues showed that the magnitude of the inotropic responses were all paralleled by quantitatively equivalent changes in the ratio cyclic AMP/cyclic GMP.…”

A modulatory octopaminergic neurone increases cyclic nucleotide levels in locust skeletal muscle.

“…The time course of the increase in cyclic AMP levels induced in the extensor muscle by exposure to octopamine has many similarities with those of the neurotransmittermediated and hormonally mediated increases in cyclic AMP levels in other tissues, including the effects of 5-HT on blowfly salivary glands (Prince, Berridge & Rasmussen, 1972;Berridge & Heslop, 1982), the effects of diuretic hormone on Rhodnius Malpighian tubules (Aston, 1975), the effects of ATP on frog ventricles (Flitney & Singh, 1980) and the effects off-adrenergic stimulation on rat erythrocytes (Clayberger, Goodman & Rasmussen, 1981). In these cases there is a rapid increase in cyclic AMP levels due to the activation of adenylate cyclase, followed by a decline which is suggested to be due to the parallel activation of phosphodiesterase activity (Berridge & Heslop, 1982).…”

Differentiation of inotropic action from chronotropic action of sympathetic agents in cultured cells of chick embryonic ventricles.

“…It was probable that injected cAMP diffused to neighboring cells within a cell aggregate through close junctions, as was proved for adult Purkinje fibers (TsIEN and WEINGART, 1976). Thereofore, several minutes of injection time would be enough to obtain the effective concentration of the order of 10-6 M FABIATO, 1975, 1978;FLITNEY and SINGH, 1980). RESULTS 1.…”