NEUROPEPTIDE-GAMMA - A MAMMALIAN TACHYKININ ENDOWED WITH POTENT ANTIDIPSOGENIC ACTION IN RATS

Neuropeptide gamma (NP gamma) is a 21 aminoacid peptide belonging to t he tachykinin (TK) family and including neurokinin A (NKA) in its C-te rminal sequence. NP gamma possesses higher affinity than NKA for centr al NK-2 receptors; it shows lower affinity for NK-1 receptors, however , it potently stimulates salivary secretion, which is mediated by NK-1 receptor activation. Pulse intracerebroventricular (pICV) injection o f TKs selectively inhibits water intake in rats. Our studies have sugg ested that NK-1 receptors may mediate the inhibition of angiotensin II -induced drinking, while NK-2 receptors that of drinking induced by ce ll dehydration. The present study evaluated the effect of pICV injecti ons of NP gamma on water intake in rats. The injection of NP gamma, 8- 250 ng/rat, markedly inhibited angiotensin II-induced drinking, and it s effect was blocked by the NK-1 receptor antagonist WIN 62577. NP gam ma potently inhibited also drinking induced by SC hypertonic NaCl load or water deprivation. The threshold dose for these effects was 31 ng/ rat. Also carbachol-induced drinking was inhibited, but at higher dose s. On the other hand, NP gamma did not modify food intake in food depr ived rats or 0.1% saccharin intake in water and food sated rats, at th e same doses effective on drinking. Present findings support the idea that TKs selectively inhibit water intake in rats and are in keeping w ith our hypothesis that NK-1 and NK-2 receptors mediate, respectively, inhibition of angiotensin II- and cell dehydration-induced drinking. In comparison to the nonmammalian TKs eledoisin and physalaemin, which proved to be the most potent antidipsogens in rats among the TKs so f ar tested, NP gamma shows similar spectrum of antidipsogenic action an d, on a molar basis, similar potency of action. These findings suggest that NP gamma may be the most important mammalian TK in the control o f water intake in the rat.