BETA-ADRENERGIC SIGNAL-TRANSDUCTION IN FISH - INTERACTIVE EFFECTS OF CATECHOLAMINES AND CORTISOL

The elevation of plasma catecholamine levels during acute stress initi ates a series of compensatory physiological and biochemical mechanisms to alleviate the disruptive effects of stress on blood oxygen transpo rt. Of particular importance is the beta-adrenergic activation of a Na + /H + antiporter associated with the red blood cell (rbc) membrane. Upon activation, the Na + /H + antiporter extrudes H + from the rbc an d the resultant alkalinization of the rbc interior serves to enhance b oth the affinity and the capacity of haemoglobin O2 binding. The activ ation of the Na + /H + exchanger is dependent upon the intracellular a ccumulation of cyclic AMP. The extent of cyclic AMP accumulation is de termined, in part, by the number and/or affinities of cell surface bet a-adrenoreceptors. Recent studies have shown that the number of cell s urface beta-adrenoreceptors are rapidly increased during acute hypoxia and that this phenomenon may explain the enhanced responsiveness of h ypoxic rbc's to exogenous catecholamines. In certain instances, plasma catecholamine and cortisol levels rise concurrently. We recently have shown that chronic (10 day) elevation of cortisol levels, in vivo, or short-term (24h) elevation, in vitro, caused significant elevation of internalized beta-adrenoreceptors. Upon exposure of the rbc's to hypo xia, these additional receptors are rapidly recruited to the cell surf ace where they become functionally coupled to adenylate cyclase. Ultim ately, therefore, chronic elevation of plasma cortisol levels increase s the responsiveness of the rbc to circulating catecholamines. We rece ntly have identified similar enhancement of cell surface beta-adrenore ceptors by cortisol and increased physiological responsiveness (glycog enolysis) to catecholamines in trout hepatocytes. Thus, chronic elevat ion of cortisol levels appears to be generally adaptive for increasing the sensitivity of the beta-adrenergic signal transduction system of at least two cell types (rbc's, hepatocytes) involved in the ameliorat ion of acute stress when plasma catecholamine levels rise.