Actions of amylin on subfornical organ neurons and on drinking behavior inrats

Amylin, a peptide hormone secreted by pancreatic beta-cells after food inta ke, contributes to metabolic control by regulating nutrient influx into the blood, whereas insulin promotes nutrient efflux and storage. We now report that amylin activates neurons in the subfornical organ (SFO), a structure in which the lack of a functional blood-brain barrier and the presence of a high density of amylin receptors may render it accessible and sensitive to circulating amylin. In an in vitro slice preparation of the rat SFO, 73% o f 78 neurons were excited by superfusion with rat amylin (10(-8)-10(-7) M); the remainder were insensitive. The threshold concentration for the excita tory response of amylin was <10(-8) M and thus similar in potency to a prev iously reported excitatory effect of ANG II on the same neurons. The excita tory effect of amylin was completely blocked by coapplication of the select ive amylin receptor antagonist AC-187 (10(-6)-10(-5) M) but was not affecte d by losartan (10(-5) M). Subcutaneous injections of 40 nmol of amylin sign ificantly increased water intake in euhydrated rats, as did an equimolar do se of ANG II, which is a well-described SFO-mediated effect of circulating ANG II. These results point to the SFO as a sensory central nervous target for amylin released systemically in response to metabolic changes. Furtherm ore, we suggest that amylin release during food intake may stimulate prandi al drinking.