Potassium Release Mediated by the Epinephrine α-Receptor in Rat Parotid Slices

Abstract

Epinephrine caused rapid release of intracellular K⁺ by acting on an α-adrenergic receptor in rat parotid gland slices. Continuous measurement by a K⁺-selective electrode served as an assay for the α-adrenergic response. The reaction reached a plateau 3 to 5 min after epinephrine addition when 30 to 50% of the K⁺ which had been in the slices was released. Isoproterenol, which is specific for β-adrenergic receptors and causes amylase secretion from the slices, did not induce K⁺ release. The concentration of epinephrine which caused a half-maximal K⁺ release was 15 µm, whereas the concentration which caused a half-maximal rate of amylase secretion in the same system was almost two orders of magnitude lower (0.2 µm).

The hypothesis that the α-adrenergic response is mediated by a reduction in the intracellular cyclic adenosine 3',5'-monophosphate (cAMP) level was tested. Preincubation with isoproterenol which activated the adenyl cyclase did not inhibit K⁺ release induced by subsequent addition of epinephrine. There was also no inhibition of K⁺ release when the slices were preincubated with N⁶-monobutyryl cAMP which acted as an efficient inducer of enzyme secretion in this system. Furthermore, the initial rise in the intracellular cAMP level caused by epinephrine was found to be the same whether or not the α-receptor was blocked by phentolamine. A subsequent more rapid decline of the cAMP level in absence of phentolamine seemed to be due to indirect effects of the α-receptor which causes extensive vacuolation in addition to K⁺ release. The experiments suggest that the α-adrenergic response is not mediated by changes in the concentration of cAMP in the cell. Electron microscopy showed that phenylephrine which activates the α-adrenergic receptor causes extensive vacuolation of the acinar gland cells. Isoproterenol and N⁶-monobutyryl cAMP cause fusion of the secretory granules with the cell membrane facing the lumen but no vacuolation. The findings substantiate and extend our previous evidence that both α- and β-adrenergic receptors reside in the same acinar cells. Injection of tyramine and phenylephrine into rats produced larger volumes of saliva than injection of isoproterenol. It is therefore suggested that K⁺ release mediated by the α-receptor is associated with water transport which sweeps the secretory protein from the acinar lumen into the gland ducts.