Nerve growth factor regulates HCO3- absorption in thick ascending limb: modifying effects of vasopressin.
Growth factors stimulate Na+/H+ exchange activity in many cell types but their effects on acid secretion via this mechanism in renal tubules are poorly understood. We examined the regulation of HCO3- absorption by nerve growth factor (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs HCO3- via apical membrane Na+/H+ exchange. MTAL were perfused in vitro with 25 mM HCO3- solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath decreased HCO3- absorption from 13.1 +/- 1.1 to 9.6 +/- 0.8 pmol.min-1.mm-1 (P < 0.001). In contrast, with 10(-10) M arginine vasopressin (AVP) in the bath, addition of NGF to the bath increased HCO3- absorption from 8.0 +/- 1.6 to 12.5 +/- 1.3 pmol.min-1.mm-1 (P < 0.01). Both effects of NGF were blocked by genistein, consistent with the involvement of tyrosine kinase pathways. However, the AVP-dependent stimulation required activation of protein kinase C (PKC), whereas the inhibition was PKC independent, indicating that the NGF-induced signaling pathways leading to inhibition and stimulation of HCO3- absorption are distinct. Hypertonicity blocked the inhibition but not the AVP-dependent stimulation, suggesting that hypertonicity and NGF may inhibit HCO3- absorption via a common mechanism. These data demonstrate that NGF inhibits HCO3- absorption in the MTAL under basal conditions but stimulates HCO3- absorption in the presence of AVP, effects that are mediated through distinct signal transduction pathways. They also show that AVP is a critical determinant of the response of the MTAL to growth factor stimulation and suggest that NGF can either inhibit or stimulate apical Na+/H+ exchange activity depending on its interactions with other regulatory factors. Locally produced growth factors such as NGF may play a role in regulating renal tubule HCO3- absorption.
Good
D W
DW
Department of Medicine, University of Texas Medical Branch, Galveston 77555, USA.
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001639:Bicarbonates / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology; D008138:Loop of Henle / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology
D001639:Bicarbonates; D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D009414:Nerve Growth Factors; D012076:Renal Agents; D001127:Arginine Vasopressin; D019833:Genistein; D011493:Protein Kinase C