Beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP.
Activation of beta-adrenergic and somatostatin receptors increases and attenuates, respectively, cAMP. We have determined, however, that in enteric endocrine cells beta-adrenergic and somatostatin receptors also regulate Na-H exchange activity, independent of their effects on cAMP. In cells loaded with a pH-sensitive dye, epinephrine, acting at a beta 2-adrenergic receptor induced an alkalinization while somatostatin caused an acidification of intracellular pH (pHi). These pHi changes were dependent on extracellular Na+ and inhibited by amiloride. Forskolin, dibutyryl-cAMP and 8-bromo-cAMP, however, had no effect on pHi. Cholera toxin, while decreasing the EC50 for epinephrine-stimulated increases in cAMP, had no effect on epinephrine-induced alkalinization, suggesting receptor coupling to Na-H exchange was not mediated by a cholera toxin-sensitive stimulatory GTP-binding protein (Gs). Additionally, epinephrine stimulated Na-H exchange in cyc- variants of S49 lymphoma cells, which lack a fundamental Gs. In the presence of pertussis toxin, somatostatin attenuation of cAMP was completely reversed; however, somatostatin inhibition of Na-H exchange was not affected. We suggest that beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of changes in cAMP and possibly independent of GTP-binding proteins previously described as being coupled to these receptors.
Barber
D L
DL
Department of Surgery/Section of Anatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
McGuire
M E
ME
Ganz
M B
MB
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008223:Lymphoma; D037342:Pertussis Toxin; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D017481:Receptors, Somatostatin; D012964:Sodium / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013004:Somatostatin; D003994:Bucladesine; D000584:Amiloride; D002772:Cholera Toxin; D012964:Sodium; D011433:Propranolol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D004837:Epinephrine