Proceedings of The Physiological Society

AstraZeneca (2010) Proc Physiol Soc 18, C03 and PC03

Oral Communications

Hemopressin is a novel peptide ligand at CB1 cannabinoid receptors that reduces appetite in rodents

G. T. Dodd1, G. Mancini2, B. Lutz2, S. M. Luckman1

1. Faculty of Life Science, The University of Manchester, Manchester, United Kingdom. 2. Johannes Gutenberg Institute, University of Mainz, Mainz, Germany.

Hemopressin is a short, nine-amino acid peptide, derived from the alpha chain of haemoglobin, which has previously been shown to cause negligible decreases in blood pressure and to have non-opioid antinociceptive effects (Heimann et al. 2007). Hemopressin acts in vitro to functionally antagonise CB1 receptors, and to potentially behave as a CB1 inverse agonist. We show that injection of hemopressin (peripheral (500 nmol/kg, i.p.) or central (10 nmol/animal, i.c.v.); animals were implanted stereotaxically with guide cannulae into the right lateral ventricle (0.2 mm posterior, 1 mm lateral from bregma for mice, and 0.8 mm posterior, 1.5 mm lateral from bregma for rats) under 2% isoflurane in 1 l/min oxygen) causes a dose-dependent decrease in normal, night-time feeding in outbred mice and rats, occurring without disrupting the normal behavioural satiety sequence, and without causing any obvious, adverse events (Dodd et al. 2010). In fact, hemopressin-induced hypophagia maintains the sequence, but surprisingly shifts it to the left, as has been seen previously with physiological satiety factors. The systemic route of administration was repeated in fasted wildtype and CB1 receptor knockout mouse littermates. Firstly, hemopressin (500nmol/kg, i.p.) decreased food intake in fasted wildtype mice, showing that it is capable of overcoming a powerful, natural orexigenic drive. Secondly, this response is lost in the CB1-/- mice. Furthermore, hemopressin (10nmol/animal, i.c.v.) can block CB1 agonist-induced hyperphagia (CP55940, 0.06 mg/kg, i.p.) in rats, providing further evidence for antagonism of the CB1 receptor in vivo (Dodd et al. 2009). We speculate that hemopressin may act as an endogenous peptide antagonist at CB1 receptors, capable of modulating appetite pathways in the brain.

Where applicable, experiments conform with Society ethical requirements