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Orexin-A and orexin-B (the hypocretins) are recently described neuropeptides suggested to have a physiological role in the regulation of food intake in the rat. We compared the orexigenic effect of the orexins administered intracerebroventricular (ICV) with other known stimulants of food intake, one strong, neuropeptide Y (NPY), and two weaker, melanin-concentrating hormone (MCH) and galanin. Orexin-A consistently stimulated food intake, but orexin-B only on occasions. Both peptides stimulated food intake significantly less than NPY, but to a similar extent to MCH (2 h food intake: NPY 3 nmol, 7.2+/-0.9 g vs saline, 1.5+/-0.2 g, P<0.001, MCH 3 nmol, 3.2+/-0.8 g vs saline, P<0.01, orexin-B 30 nmol, 2. 6+/-0.5 g vs saline, P=0.11) and to galanin (1 h food intake: galanin 3 nmol, 2.0+/-0.4 g vs saline, 0.8+/-0.2 g, P<0.05, orexin-A 3 nmol 2.2+/-0.4 g vs saline, P<0.01; 2 hour food intake: orexin-B 3 nmol, 2.4+/-0.3 g vs saline, 1.3+/-0.2 g, P<0.05). Following ICV orexin-A, hypothalamic c-fos, a maker of neuronal activation, was highly expressed in the paraventricular nucleus (PVN), and the arcuate nucleus (P<0.005 for both). IntraPVN injection of orexin-A stimulated 2 h food intake by one gram (orexin-A 0.03 nmol, 1.6+/-0. 3 g vs saline, 0.5+/-0.3 g, P<0.005). These findings support the suggestion that the orexins stimulate food intake. However, this effect is weak and may cast doubt upon their physiological importance in appetite regulation in the rat.

Intravenous infusions of glucagon‐like peptide‐1(7‐36) amide (GLP‐1; 35 pmol min‐1 kg‐1 for 10 min) produced a significant rise in mean heart rate, without significant change in mean aortic blood pressure, together with a significant rise in mean arterial plasma insulin, but not in plasma pancreatic glucagon or pancreatic polypeptide concentration, in conscious calves given exogenous glucose (30‐60 micromol min‐1 kg‐1 i.v.). The insulinotropic effect was eliminated in the presence of exogenous amino acids (0.03 mmol min‐1 kg‐1 i.v.). It was not affected predictably by blocking the synthesis of nitric oxide or by the simultaneous administration of the established incretin factor gastrin‐releasing peptide (GRP). Whereas GLP‐1 produced a statistically significant rise in plasma insulin concentration in these animals, it was much less effective than GRP in this respect, when given by continuous i.v. infusion.

Concentrations of plasma arginine vasopressin (AVP) were studied in patients receiving chemotherapy. Of the 18 patients studied, nine experienced nausea and vomiting and the remaining nine were nonvomiters who suffered at worst mild nausea. Plasma AVP in the non-vomiting group remained within the normal range (0.5-1.5 pmol 1(-1] throughout the sampling period. However, patients who vomited showed (with one exception) substantial rises in AVP ranging from 4 to 129-fold. Plasma AVP concentrations were outside the normal range in vomiters and were higher than in non-vomiting patients at 3 h (P less than 0.05) and 5h (P less than 0.01) after chemotherapy. One patient was sampled during consecutive treatment courses, once as a vomiter and once as a non-vomiter; results demonstrated a 16-fold rise in AVP as a vomiter and no rise as a non-vomiter. Significant changes in plasma AVP levels were also observed in patients who suffered moderate or severe nausea compared to those who had mild or no nausea (P less than 0.05). Plasma AVP may prove to be a good objective marker for nausea in future anti-emetic trials.