DECREASED M(3)-MUSCARINIC AND ALPHA(1)-ADRENERGIC RECEPTOR STIMULATION OF PIP2 HYDROLYSIS IN PAROTID-GLAND MEMBRANES FROM AGED RATS - DEFECT IN ACTIVATION OF G(ALPHA-Q 11)/

m(3)-Muscarinic cholinergic receptor (m(3)-AChR) and alpha(1)-adrenerg ic receptor (alpha(1)-AR) stimulation of phosphatidylinositol 4,5-bisp hosphate (PIP2) hydrolysis (by a PIP2-specific phospholipase C, PLC) i n rat parotid gland membranes is mediated via activation of alpha subu nits of the G(q/11) family of G-proteins, This study examines m(3)-ACh R and alpha(1)-AR stimulation of PIP2 hydrolysis in membranes isolated from parotid glands of old (24 months) and young (3 months) rats (old and young rat membranes), Old rat membranes exhibited reduced stimula tion of PIP2 hydrolysis in response to the addition of guanosine-5'-O- (3-thiotrisphosphate) (GTP gamma S) alone or GTP gamma S plus either c arbachol (m(3)-AChR agonist) or epinephrine (alpha(1)-AR agonist), Thi s reduction in receptor-stimulated PIP2 hydrolysis was not due to a de crease in PLC activity per se since cholate-solubilized PLC activity w as similar in old and young rat membranes, Additionally, these membran es exhibited comparable, immunologically detectable, levels of PLC bet a(3), G alpha(q/11), and G(beta). In the presence of 10 mu M AlCl3 and 10 mM NaF, stimulation of PIP2 hydrolysis in both old and young rat m embranes was similar, Preincubation of membranes from old rats with GT P gamma S induced a time-dependent increase in the rate of PIP2 hydrol ysis and, with 20 min preincubation, the rates of hydrolysis in old an d young rat membranes were not statistically different, In aggregate, these data indicate that there is a defect in the activation of G(alph a q/11) in parotid gland membranes from old rats. (C) 1995 Academic Pr ess, Inc.