Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that parathyroid hormone (PTH)-(1-34) or its analogue PTH-(3-34) inhibits proximal tubule (PT) Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity independently of adenosine 3',5'-cyclic monophosphate generation. The present study used PT suspensions to investigate the signaling pathway responsible for this hormonal action. PTH-(1-34) and PTH-(3-34) significantly increased the release of arachidonic acid (AA) compared with control tubules, suggesting activation of phospholipase A2 (PLA2). AA, 10(-6) M, mimicked the inhibition of the pump by 10(-8) M PTH-(3-34), and together were not additive. Eicosatetraynoic acid, 3 microM, a general inhibitor of AA metabolism, blocked the PTH action. Indomethacin, 10 microM, an inhibitor of AA-dependent cyclooxygenase, did not prevent the PTH action, but 2 microM 7-ethoxyresorufin, a cytochrome P-450 inhibitor, prevented the PTH effect. 20-Hydroxyeicosatetraenoic acid (20-HETE), the main product of P-450 metabolism in PT, inhibited Na(+)-K(+)-ATPase activity to the same extent as 10(-8) M PTH-(3-34), was not additive with PTH, and was maximally inhibitory at 10(-7) M. To further investigate the signaling pathway responsible for PTH-activated PLA2, we tested the effect of PTH on cytoplasmic free Ca2+ ([Ca2+]i). PTH-(1-34), 10(-7) M, did not affect [Ca2+]i, although 10(-8) M angiotensin II promoted a Ca2+ transient. Treatment of PT with pertussis toxin (PTX) did not prevent the PTH action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone inhibits Na(+)-K(+)-ATPase through a cytochrome P-450 pathway. 816 Aug

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.
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PMID:Transducing pathways involved in the control of NaCl reabsorption in the thick ascending limb of Henle's loop. 955 29