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Structure and activity of OK-GC: a kidney receptor guanylate cyclase activated by guanylin peptides

London, RM and Eber, SL and Visweswariah, SS and Krause, WJ and Forte, LR (1999) Structure and activity of OK-GC: a kidney receptor guanylate cyclase activated by guanylin peptides. In: American Journal Of Physiology-Renal Physiology, 276 (6). F882-F891.

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Official URL: http://ncsi-net.ncsi.iisc.ernet.in/gsdl/cgi-bin/li...

Abstract

Uroguanylin, guanylin, and lymphoguanylin are small peptides that activate renal and intestinal receptor guanylate cyclases (GC). They are structurally similar to bacterial heat-stable enterotoxins (ST) that cause secretory diarrhea. Uroguanylin, guanylin, and ST elicit natriuresis, kaliuresis, and diuresis by direct actions on kidney GC receptors. A 3,762-bp cDNA characterizing a uroguanylin/guanylin/ST receptor was isolated from opossum kidney (OK) cell RNA/cDNA. This kidney cDNA (OK-GC) encodes a mature protein containing 1,049 residues sharing 72.4-75.8% identity with rat, human, and porcine forms of intestinal GC-C receptors. COS or HEK-293 cells expressing OK-GC receptor protein were activated by uroguanylin, guanylin, or ST13 peptides. The 3.8-kb OK-GC mRNA transcript is most abundant in the kidney cortex and intestinal mucosa, with lower mRNA levels observed in urinary bladder, adrenal gland, and myocardium and with no detectable transcripts in skin or stomach mucosa. We propose that OK-GC receptor GC participates in a renal mechanism of action for uroguanylin and/or guanylin in the physiological regulation of urinary sodium, potassium, and water excretion. This renal tubular receptor GC may be a target for circulating uroguanylin in an endocrine link between the intestine and kidney and/or participate in an intrarenal paracrine mechanism for regulation of kidney function via the intracellular second messenger, cGMP.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Amer Physiological Society.
Keywords: guanosine 3;5 -cyclic monophosphate;uroguanylin;OK cells.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Date Deposited: 30 Jun 2011 07:28
Last Modified: 03 Aug 2011 07:00
URI: http://eprints.iisc.ernet.in/id/eprint/38800

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