title: The lysine-1 analog of guanylin induces intestinal secretion and natriuresis in the isolated perfused kidney.
abstract: Guanylin is an endogenous peptide synthesized by several mammalian species that mimics the effects of a thermostable enterotoxin of Escherichia coli (STa: NTFYCCELCCNPACAGCY) in the gut. We have cloned a lysine-1 derivative of rat guanylin (Lys-1-NTCEICAYAACTGC) and tested its effects on ileal tissue membranes in Ussing chambers and in the isolated perfused rat kidney. Rabbit ileal mucosa membranes were mounted into a Ussing chamber and the effects of Lys-1 guanylin (Lys-1 G) and STa enterotoxin peptide on chloride secretion were determined by changes in short-circuit current (Isc). Lys-1 G (10 to 100 nM) showed a dose-dependent effect on chloride secretion with a maximal response estimated to be 52 microA/cm2. Lys-1 G mimics the effect of STa peptide, but the enterotoxin elicited a greater maximal effect of 120 microA/cm2 (P < 0.01). Lys-1 G (2.5 micrograms/ml) promoted an increase in both urine flow (from 0.13 +/- 0.07 to 0.40 +/- 0.01 ml g-1 min-1, N = 4; P < 0.05) and glomerular filtration rate (from 0.68 +/- 0.02 to 0.85 +/- 0.00 ml g-1 min-1, N = 4; P < 0.01) in the isolated perfused kidney and a reduction of the fractional reabsorption of sodium (from 76.0 +/- 0.03 to 59.5 +/- 0.85%, N = 4; P < 0.01). These maximal effects were accompanied by intense natriuretic effect observed 30 and 60 min after drug administration. The Lys-1 G analog similar to STa enterotoxin elicited intestinal chloride secretion and a natriuretic effect. These data demonstrate that the cloned peptide analog retains the biological activity of the native hormone and presents activity similar to STa. The properties of Lys-1 G resemble those of a factor formed during perfusion of the hypoxic rabbit kidney and named by us factor natriureticus similis (FNS).
authors.affiliation: Divisão de Farmacologia Renal e Metabólica, Hospital Universitário Walter Cantídeo, Fortaleza, Brasil. upc@lia.ufc.br
authors.forename: M C
authors.initials: MC
authors.lastname: Fonteles
authors.forename: H S
authors.initials: HS
authors.lastname: Monteiro
authors.forename: A M
authors.initials: AM
authors.lastname: Soares
authors.forename: M S
authors.initials: MS
authors.lastname: Santos-Neto
authors.forename: R N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: A A
authors.initials: AA
authors.lastname: Lima
mesh_terms: D000818:Animals; D005260:Female; D005768:Gastrointestinal Hormones; D007419:Intestinal Secretions / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008239:Lysine / Q000031:analogs & derivatives*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D045265:Natriuretic Peptides; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism
chemical_list: D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; C072685:guanylin; D012964:Sodium; D008239:Lysine