Agonist-induced activation of Na+/H+ exchange in rat parotid acinar cells.
The present studies were designed to test our previous suggestion that Na+/H+ exchange was activated by muscarinic stimulation of rat parotid acinar cells. Consistent with this hypothesis, we demonstrate here that intact rat parotid acini stimulated with the muscarinic agonist carbachol in HCO3- -free medium show an enhanced recovery from an acute acid load as compared to similarly challenged untreated preparations. Amiloride-sensitive 22Na uptake, due to Na+/H+ exchange, was also studied in plasma membrane vesicles prepared from rat parotid acini pretreated with carbachol. This uptake was stimulated two-fold relative to that observed in vesicles from control (untreated) acini. This stimulation was time dependent, requiring approximately 15 min of acinar incubation with carbachol to reach completion, and was blocked by the presence of the muscarinic antagonist atropine (2 x 10(-5) M) in the pretreatment medium. The effect of carbachol was dose dependent with K0.5 approximately 3 x 10(-6) M. Stimulation of the exchanger was also seen in vesicles prepared from acini pretreated with the alpha-adrenergic agonist epinephrine, but not with the beta-adrenergic agonist isoproterenol, or with substance P. Kinetic analysis indicated that the stimulation induced by carbachol was due to an alkaline shift in the pH responsiveness of the exchanger in addition to an increased apparent transport capacity. Taken together with previous results from this and other laboratories, these results strongly suggest that the Na+/H+ exchanger and its regulation are intimately involved in the fluid-secretory response of the rat parotid.
Manganel
M
M
Clinical Investigations Branch, National Institutes of Health, Bethesda, Maryland 20892.
Turner
R J
RJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D001285:Atropine; D006859:Hydrogen; D002217:Carbachol; D012964:Sodium