Renal effects.
Amylin bound to kidney cortex in a distinctive pattern. Binding appeared specific in that it was displaceable with amylin antagonists. It was associated with activation of cyclic AMP (cAMP), and was thereby likely to represent receptor binding and activation. Amylin's principal effects at the kidney included a stimulation of plasma renin activity, reflected in aldosterone increases at quasi-physiological amylin concentrations. It was unclear whether this was a local or a systemic effect. Other renal effects in rats included a diuretic effect and a natriuretic effect. The latter was mainly driven by the diuresis, since urinary sodium concentration did not change. Amylin had a transient effect to lower plasma potassium concentration. This effect was likely to be a consequence of activation of Na+/K+-ATPase, an action shared with insulin and catecholamines. Amylin lowered plasma calcium, particularly ionized calcium, likely due to an antiresorptive effect at osteoclasts. Immunoreactive amylin was detected in the developing kidney. It appeared to have a trophic effect in kidney, and its absence resulted in renal dysgenesis. Neurons in the subfornical organ (SFO), which has a role in fluid/electrolyte homeostasis, were potently activated by amylin. The dipsogenic and renal effects of amylin may be related to effects at the SFO.
Amylin Pharmaceuticals, Inc., San Diego, California, USA.
Andrew
A
Young
D000450:Aldosterone / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D013356:Subfornical Organ / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D000450:Aldosterone