Enterostatin suppresses food intake in rats after near-celiac and intracarotid arterial injection

Enterostatin (Ent) selectively suppresses the intake of dietary fat after p eripheral and central administration. To further investigate the site of ac tion of Ent, we compared the feeding responses to Ent injected intra-arteri ally near the celiac artery, into the carotid artery, or intravenously in r ats adapted to a high-fat diet. After near-celiac arterial injection there was an immediate dose-dependent (0.05-13.5 nmol) inhibition of food intake occurring within 5 min in overnight-fasted rats that lasted up to 20 min. C arotid arterial Ent had a similar, immediate dose-related response, and the inhibitory effect was long lasting. The response to intravenous Ent was on ly evident at the highest dose (13.5 nmol) and was delayed for at least 120 min. Pretreatment with capsaicin, which causes degeneration of vagal senso ry neurons, abolished the inhibitory responses to near-celiac Ent but not t o intravenous or intracarotid Ent. These results provide further evidence f or both a gastrointestinal site of action for peripheral Ent and a central site of action for intracarotid Ent and suggest that the delayed response t o intravenous Ent may reflect either binding or slow uptake of this peptide into the central nervous system.