Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanyiin are peptides that bind to and activate guanylate c yclase C and control salt and water transport in many epithelia in vertebra tes, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic ef fects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat k idney to identify possible synergisms between ANP, guanylin and uroguanylin . Inulin was added to the perfusate and glomerular filtration rate (GFR) wa s determined at 10-min intervals. Sodium was also determined. Electrolyte d ynamics were measured by the clearance formula. Guanylin (0.5 mu g/ml, N = 12) or uroguanylin (0.5 mu g/ml, N = 9) was added to the system after 30 mi n of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min inter vals to a control CN = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 mu g/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 +/- 0.86 to 64.62 +/- 1.92, 120 min). In contrast, ANP blocked uroguanylin-indu ced increase in urine flow (from 0.21 +/- 0.01 to 0.15 +/- 0.007 mi g(-1) m in(-1), 120 min, P<0.05) and the reduction in fractional sodium transport ( from 72.04 +/- 0.86 to 85.19 +/- 1.48, %TNa+, at 120 min of perfusion, P<0. 05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.