Bv8, the amphibian homologue of the mammalian prokineticins, modulates ingestive behaviour in rats

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Abstract
The small protein Bv8, secreted by the skin of the frog Bombina variegata, belongs to a novel family of secreted proteins whose mammalian orthologues have been identified and named prokineticins (PK‐1 and PK‐2). Bv8 (from 2.5 to 60 pmol) injected into the lateral ventricles of rat brain suppressed diurnal, nocturnal, deprivation‐induced and neuropeptide Y‐stimulated feeding and stimulated diurnal drinking. Nocturnal drinking was increased only in fasted rats. PK‐2 mRNA is expressed in discrete areas of the rat brain, including the suprachiasmatic nucleus (SCN), medial preoptic area (MPA) and nucleus of the solitary tract (NTS). In the SCN neurons, PK‐2 mRNA is highest during the light phase of the circadian cycle and undetectable during the dark phase. The G‐protein‐coupled receptor prokineticin receptor 2 (PKR‐2), which binds Bv8 and PK‐2 with high affinity, is mainly expressed in the piriform cortex, paraventricular thalamic nucleus, parataenial nucleus (PT), SCN, hypothalamic paraventricular (PVH) and dorsomedial (DMH) nuclei, arcuate nucleus (ARC) and subfornical organ (SFO) of the rat brain. Bv8 microinjected into the ARC, at doses from 0.02 to 2.0 pmol during night‐time or from 0.2 to 5 pmol in 24‐h‐fasted rats, selectively suppressed feeding without affecting drinking. When injected into the SFO, Bv8 (from 0.2 to 2 pmol) stimulated drinking but did not affect feeding. Bv8 injections into other brain areas left rat ingestive behaviours unchanged. We hypothesize that PK‐2‐rich projections from SCN neurons to PKR‐expressing ARC neurons could transmit the circadian rhythm of feeding, whereas inputs from the PK‐2‐expressing NTS neurons to the PKR‐2‐expressing SFO neurons could transmit visceral information on the water–electrolyte balance and osmotic regulation. British Journal of Pharmacology (2004) 142, 181–191. doi:10.1038/sj.bjp.0705686