AÃÃes farmacolÃgicas da ser-thr-lys-guanilina em sistema de perfusÃo de rim isolado de rato / Pharmacological actions of ser-thr-lys-guanilina in isolated perfused rat kidney

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

25/07/2005

RESUMO

Guanylin and uroguanylin are members of a family of peptides that stimulates cGMP production in several organic tissues, as intestine, kidney, airway, linfonodes, testis, brain and adrenal medulla (Field et a.l., 1978; Forte et al., 1988, 1989; Hamra et al., 1993; Schulz et al., 1992). Their 15 amino acid structures have been identified from rat intestine and opossum urine, respectively (Currie et al., 1992; Hamra et al., 1993), and they seem to be the link between intestine and kidney functions in controling blood pressure, as the âintestinal natriuretic hormoneâ suggested by some authors (Carey, 1978; Lennane et al., 1975). It was demonstrated that a Lysine-1 analog of guanylin is a more potent natriuretic and kaliuretic peptide. The aim of this study was to evaluate the renal effects of a novel analog of guanylin: ser-thr-lys-guanylin. Its effects were examined using isolated perfused kidneys from Wistar rats. All experiments were preceded by a 30 minutes internal control period and an external control group (C), in which the kidneys were perfused only with Krebs-Henseleit solution containing 6g% of a previously dialysed bovine albumine serum. The data was analyzed by Student t-test and ANOVA. The level of significance was set at p<0,05. Ser-thr-lys-guanylin, at the lowest dose (0.1 Âg/mL) and uroguanylin (0.5Âg/mL) caused similar effects. Both groups were able to increase perfusion presure (PP: 101.5Â3.7 to 111Â2.9mmHg; 101.2Â2.6 to 113.4Â2.5 mmHg), urinary flow (UF: 0.158Â0.016 to 0.223Â0.019 mL.g-1.min-1; 0.16Â0.016 to 0.226Â0.2mL.g-1.min-1) and to decrease sodium (%TNa+: 0.774Â0.06 to 0.724Â0.035; 0.735Â0.065 to 0.773Â0.084), potassium (%TK+: 66.89Â2.77 to 47.29Â3.34; 63.54Â3.82 to 42.54Â8.14) and cloride (%TCl-: 85.69Â1.19 to 73.59Â2.63) tubular reabsorption. Similar effects were also found in response to the Escherichia coli heat-stable enterotoxin (STa), guanylin, uroguanylin and lys-guanylin in the same system (Lima et al., 1992; Fonteles et al., 1996 e 1998). However, a greater dose (1Âg/mL), not only caused signifcantly decrease in the urinary flow (UF: 0.165Â0.004 to 0.111Â0.009 mL.g-1.min-1), but was also able to block the diuretic effects of uroguanylin (UF: 0.168Â0.004 to 0.116Â0.006 mL.g-1.min-1), although it still decreased potassium (%TK+: 72.29Â1.2 to 49.73Â6.75) and cloride(%TCl-: 85.96Â0.79 to 81.9Â1.47) tubular reabsorption. The precise renal mecanism of action of this family of peptides has not yet been fully elucidated. Deletion of GC-C genes in transgenic mice reveals that intestinal fluid secretion responses to STa are completely lost (Schulz et al., 1997 &Mann et al., 1997), but the natriuretic responses to STa and uroguanylin are retained (Carrithers et al., 1999), suggesting that other receptors are envolved. There is a possibility that there are to peptides causing antagonic effects. Further isolation may be necessary. Further studies are required to elucidate the specific renal mechanism of action of this new peptide. The discovery of guanylin and its family has promoted significant advances in the understanding of endogenous control of salt, water and eletrolites. The study of its analogs in perfused rat kidneys could help in elucidating their specific renal mecanism of action and bring great perspectives in the control of blood pressure.

ASSUNTO(S)

farmacologia natriurÃticos insuficiÃncia renal guanilato ciclase natriuretic agents kidney failure, acute guanylate cyclase

ACESSO AO ARTIGO

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