Amylin stimulates proximal tubular sodium transport and cell proliferation in the rat kidney.
In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was associated with proximal convoluted tubules but not distal tubules, interstitium, or glomeruli in the renal cortex. Split-drop micropuncture experiments showed that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated proximal tubular fluid absorption by 28%. This effect was inhibited by luminal addition of ethylisopropylamiloride, indicating mediation by a brush-border Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187, reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role for endogenous amylin in salt homeostasis. In primary cultures of rat proximal tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the amylin binding sites in the renal cortex blocked the mitogenic action of amylin. We conclude that amylin acts on renal proximal tubules to promote sodium and water reabsorption and cell proliferation. These novel actions may have implications for the development of hypertension for example in non-insulin-dependent diabetes mellitus and obesity in which hyperamylinemia has been observed.
Harris
P J
PJ
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Cooper
M E
ME
Hiranyachattada
S
S
Berka
J L
JL
Kelly
D J
DJ
Nobes
M
M
Wookey
P J
PJ
D000042:Absorption / Q000187:drug effects; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000166:cytology* / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010477:Perfusion; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D008934:Mitogens; D000584:Amiloride; D012964:Sodium; C039614:ethylisopropylamiloride