Transducing pathways involved in the control of NaCl reabsorption in the thick ascending limb of Henle's loop.
The thick ascending limb of Henle's loop (TAL) is involved in the urinary dilution/concentration process by actively reabsorbing NaCl through a complex mechanism. Some years ago, compelling evidence was provided that cAMP stimulates NaCl reabsorption through the activation of adenylyl cyclase by several hormones other than antidiuretic hormone (ADH). Synthesis of cyclic AMP is inhibited by prostaglandin E2 (PGE2) and arachidonic acid per se, via the pertussis toxin-sensitive protein Gi activation. Cyclic GMP cascade down-regulates NaCl reabsorption, through activation of both guanylyl cyclase receptors (by ANF and urodilatin), and soluble guanylyl cyclase (by nitric oxide, NO). In TAL, NO is produced by the cytokine-inducible form of NO synthase, but not by the constitutive one. Agonists known to activate protein kinase C (PKC) in TAL elicit opposite effects on NaCl reabsorption. Five PKC isoforms belonging to the conventional, novel, and atypical enzyme subclasses have been recently defined in TAL and might differently regulate NaCl flux. Increments in intracellular calcium ([Ca2+]i) inhibit NaCl reabsorption via three pathways: (i) a possible direct effect on ion channels, (ii) a PLA2-mediated production of arachidonic acid derivatives (20-HETE), and (iii) inhibition of the ADH-induced cAMP accumulation. This last effect results from activation of phosphodiesterase (common to the agents that increase [Ca2+]i), and inhibition of adenylyl cyclase (only elicited by Ca2+c). Finally, the apical localization of some agonists effects is documented.
Bailly
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URA CNRS 1869, Département de Biologie Cellulaire et Moléculaire, CEA Saclay, France. bailly@dsvidf.cea.fr
D000042:Absorption; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008138:Loop of Henle / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction; D012965:Sodium Chloride / Q000378:metabolism*
D012965:Sodium Chloride; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium