Abstract

Norepinephrine and phenylephrine caused a rapid rise in the level of cyclic 3',5'-GMP in slices of rat parotid gland. The increase in the cyclic GMP level caused by these agents was blocked by phentolamine but not by propranolol or atropine. Isoproterenol increased the cyclic GMP level in the parotid slightly. The stimulatory effect of isoproterenol on the parotid cyclic GMP level was blocked by propranolol. Since alpha adrenergic agonists caused a much larger increase in parotid cyclic GMP levels than isoproterenol, the response was classified primarily as an alpha adrenergic response. Alpha adrenergic agonists and 8-bromo-cyclic GMP caused K⁺ release from parotid slices. Isoproterenol and dibutyryl cyclic AMP also caused K⁺ release from parotid slices, but were not nearly as effective as the alpha adrenergic agonists or 8-bromo-cyclic GMP. Increased cyclic GMP accumulation was not always associated with increased K⁺ release from parotid slices. 1-Methyl-3-isobutylxanthine potentiated the effect of limiting concentrations of phenylephrine on cyclic GMP accumulation but did not potentiate the effect of the same limiting concentrations of phenylephrine on K⁺ release. Alpha adrenergic agonists inhibited the stimulation by isoproterenol of cyclic AMP accumulation. Similarly, isoproterenol reduced the ability of phenylephrine to increase the parotid slice level of cyclic GMP. Amylase release caused by alpha adrenergic agonists and isoporterenol was less than additive, whereas the amount of K⁺ release caused by these agonists was additive. Thus the lack of additivity between the actions of alpha and beta adrenergic agonists on cyclic nucleotide levels was not always accompanied by a similar lack of additivity at the level of the physiological response.