Evidence for functional ghrelin receptors on parasympathetic preganglionic neurons of micturition control pathways in the rat.

1. Previous work indicates that agonists of ghrelin receptors can act within the spinal cord to stimulate autonomic outputs to the colorectum and to blood vessels. Because of the close relationship between colorectal and urinary bladder control, we have investigated whether ghrelin receptor agonists also stimulate spinal centres that influence the bladder. 2. The ghrelin receptor agonist capromorelin (10 mg/kg), injected intravenously in anaesthetized male rats, disrupted the ongoing cycle of micturition reflexes and caused phasic oscillations in pressure that averaged approximately 20 mmHg. Fluid output from the bladder was diminished. The effects of capromorelin were inhibited by hexamethonium (10 mg/kg bolus followed by 4 mg/kg per h infusion, i.v.) and were further reduced by atropine (5 mg/kg bolus followed by 2.5 mg/kg per h infusion, i.v.). Capromorelin (250 microg) injected directly into the spinal cord at the lumbosacral level also increased contractile activity of the bladder. However, capromorelin, up to 0.1 mmol/L, had no effect on the tension of isolated muscle strips from the bladder. Effects of intravenous capromorelin (10 mg/kg) on bladder pressure were still observed after the descending pathways in the spinal cord were disrupted at the thoracic level. 3. In situ hybridization studies revealed ghrelin receptor gene expression in neurons of the autonomic intermediolateral (IML) cell columns. Following a series of micturition reflexes elicited by infusion of saline into the bladder, the immediate early gene product c-Fos was observed in neurons of the lumbosacral IML and approximately 20% of these also expressed ghrelin receptor gene transcripts. 4. It is concluded that ghrelin receptors are expressed by lumbosacral autonomic preganglionic neurons of the micturition reflex pathways and that ghrelin receptor agonists stimulate these neurons.