Molecular Pharmacology, Vol 18, 356-361, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

-Adrenergic Regulation of Cholinergic Responses in Rat Parotid Acinar Cells

¹ Neurology Research Laboratory, Durham Veterans Administration Medical Center, and Departments of Medicine and Pharmacology, Duke University, Durham, North Carolina 27705

-Adrenergic or muscarinic cholinergic stimulation leads to a release of K⁺ from dispersed parotid acinar cells. Cells exposed to (-)-epinephrine at physiological pH in Hepes medium and then washed become refractory or densensitized to subsequent -adrenergic challenge with (-)-epinephrine and to cholinergic challenge with carbachol. This -adrenergic-elicited attenuation of the cholinergic response appears to result from a decrease in Ca²⁺ entry during cholinergic challenge since A23187 incubation releases as much K⁺ in desensitized cells as in washed controls. This desensitization occurs during (-)-epinephrine preincubation in the absence of Ca²⁺ and without K⁺ release. It is prevented if phentolamine is present. The desensitization is rapid, being complete in 2 min. Desensitization is partly reversible by incubation in fresh buffer or in the presence of phentolamine; it is completely and rapidly reversed by exposure to a high-K⁺ medium. Although the cholinergic response is attenuated after -adrenergic stimulation, the binding of [³H]quinuclidinyl benzilate is the same in these cells as in washed controls. These data suggest that the attenuated cholinergic response in -adrenergic desensitized cells results from an alteration between cholinergic receptor occupation and Ca²⁺ entry. This type of -adrenergic desensitization differs from a type described previously in these cells at lower pH in Hanks’ medium. Although both types may take place at physiological pH levels, this -adrenergic regulation of the cholinergic response is clearly an important cellular response to persistent stimulation. Since other tissues and presynaptic nerve terminals appears to have -adrenergic and muscarinic cholinergic receptors, this regulation may be an important mechanism of adaptation to continued neuronal activity.