PT  - JOURNAL ARTICLE
AU  - JAMES N. DAVIS
AU  - EDWARD OLENDER
AU  - WENDY MAURY
AU  - ROBERT MCDANIEL
TI  - α-Adrenergic Regulation of Cholinergic Responses in Rat Parotid Acinar Cells
DP  - 1980 Nov 01
TA  - Molecular Pharmacology
PG  - 356--361
VI  - 18
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/18/3/356.short
4100  - http://molpharm.aspetjournals.org/content/18/3/356.full
SO  - Mol Pharmacol1980 Nov 01; 18
AB  - α-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 α-adrenergic challenge with (-)-epinephrine and to cholinergic challenge with carbachol. This α-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 α-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 α-adrenergic desensitized cells results from an alteration between cholinergic receptor occupation and Ca2+ entry. This type of α-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 α-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 α-adrenergic and muscarinic cholinergic receptors, this regulation may be an important mechanism of adaptation to continued neuronal activity.