The mechanism of cyclic AMP stimulation of secretion in the dogfish rectal gland

Abstract

1. Cyclic AMP induces pronounced increases in ouabain binding and ouabain-sensitive oxygen consumption in rectal gland slices but does so in the absence of any change in the Na−K-ATPase activity of tissue homogenates. It is suggested that this apparent paradox results from the presence of inactive or concealed ‘latent sites’ in the membrane of the unstimulated gland which become exposed or activated in the presence of cAMP. 2. Evidence suggests that, in the absence of cAMP, the exposure and activation of these latent sites is largely determined by the rate of sodium entry into the cells. It appears that sodium can enter the cells either by a simple passive diffusion down the electrochemical gradient or via a furosemide-sensitive, chloride-coupled pathway. 3. Experiments have shown that the cAMP effect on ouabain binding and oxygen consumption is absent in conditions designed to eliminate the gradient for sodium entry into the cells. Similarly, no cAMP effect on these parameters is observed in the absence of external chloride or in the presence of furosemide. Furthermore, cAMP has been shown to produce a marked increase in sodium entry into the rectal gland cell and this enhanced entry is entirely furosemide-sensitive. 4. It appears therefore that cAMP has no direct effect on the recruitment of latent sites per se but instead has a specific, stimulatory action on the furosemide-sensitive entry of sodium which, in turn, leads to an increase in functional sodium pump sites and an enhanced sodium efflux. Chloride efflux appears to be increased in a passive manner as a result of the increased gradient on this ion subsequent to an enhanced entry via the cAMP-stimulated, furosemide-sensitive pathway.