Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent of cAMP.
We have previously determined that beta-adrenergic and somatostatin receptors stimulate and inhibit, respectively, Na-H exchange independent of changes in cAMP accumulation (Barber, D.L., McGuire, M.E., and Ganz, M.B. (1989) J. Biol. Chem. 264, 21038-21042). The present study extends our work on the beta-adrenergic receptor (beta AR) by investigating receptor activation of Na-H exchange in multiple cell types that either endogenously express the beta AR or that have been transfected with cDNA of the hamster lung beta 2AR or the turkey erythrocyte beta AR. Exchanger activity was determined by monitoring intracellular pH in cell populations loaded with the pH-sensitive dye BCECF (2,7-biscarboxyethyl-5(6)-carboxyfluorescein). In addition to the action of the beta AR, activation of prostaglandin E1 and parathyroid hormone receptors induced an intracellular alkalinization by stimulating a Na(+)-dependent amiloride-sensitive Na-H exchange. In contrast, activation of D2-dopaminergic receptors induced an intracellular acidification by inhibiting Na-H exchange. beta-Adrenergic, prostaglandin E1, and parathyroid hormone receptors activated Na-H exchange independent of changes in intracellular cAMP accumulation and independent of a cholera toxin-sensitive stimulatory GTP regulatory protein. D2-dopaminergic receptors inhibited exchanger activity independent of a pertussis toxin-sensitive inhibitory GTP regulatory protein. We suggest that these receptors are functionally coupled to adenylate cyclase and Na-H exchange through divergent signaling mechanisms.
Ganz
M B
MB
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Pachter
J A
JA
Barber
D L
DL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001254:Astrocytoma; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D004837:Epinephrine / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007739:L Cells / Q000378:metabolism; D012516:Osteosarcoma; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*; D017448:Receptors, Dopamine D2; D018016:Receptors, Parathyroid Hormone; D011982:Receptors, Prostaglandin / Q000502:physiology*; D018078:Receptors, Prostaglandin E; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D018016:Receptors, Parathyroid Hormone; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D012964:Sodium; D000262:Adenylyl Cyclases; D004837:Epinephrine