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

Abstract

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.

Identification of neurons that express ghrelin receptors in autonomic pathways originating from the spinal cord

“…Consistent with these data, in situ hybridisation histochemistry has demonstrated nerve cells expressing the ghrelin receptor gene in the autonomic preganglionic cell groups of the intermediolateral (IML) cell columns, and repetitive activation of micturition reflexes causes fos expression in preganglionic neurons of the bladder-controlling cell centres that lie in the IML and that express the ghrelin receptor gene (Ferens et al 2010b). However, not all IML neurons express the receptor gene and another investigated pathway, namely the cardio-accelerator pathway, is not activated (Ferens et al 2010a).…”

“…In contrast to in situ hybridisation histochemistry for ghrelin receptor expression, which only reveals the cell bodies (Ferens et al 2010a(Ferens et al , 2010b, because little or no gene expression occurs in the nerve terminals, we have been able to reveal terminal fields by using the reporter mice. The ability to characterise subtypes of postganglionic neurons innervated by these terminals aids in the identification of the pathways of preganglionic autonomic neurons that express the ghrelin receptor.…”

“…Studies in which ghrelin receptor agonists have been applied directly to the spinal cord have revealed three activated pathways: vasoconstrictor pathways (Shimizu et al 2006;Ferens et al 2010a), defaecation pathways (Shimizu et al 2006) and pathways that cause contraction of the bladder detrusor muscle (Ferens et al 2010b). Consistent with these data, in situ hybridisation histochemistry has demonstrated nerve cells expressing the ghrelin receptor gene in the autonomic preganglionic cell groups of the intermediolateral (IML) cell columns, and repetitive activation of micturition reflexes causes fos expression in preganglionic neurons of the bladder-controlling cell centres that lie in the IML and that express the ghrelin receptor gene (Ferens et al 2010b).…”

“…This includes the activation of preganglionic neurons in the lumbo-sacral cord by ghrelin and by ghrelin receptor agonists (Shimizu et al 2006;Hirayama et al 2010), which elicit motor patterns that result in co-ordinated the emptying of the colon. Ghrelin receptor agonists also stimulate preganglionic neurons in the thoracic and lumbar regions of the spinal cord to increase blood pressure (Shimizu et al 2006;Ferens et al 2010a) and excitatory ghrelin receptors occur on preganglionic neurons that cause contractions of the urinary bladder (Ferens et al 2010b). When the expression of ghrelin receptors in the spinal cord was examined by using in situ hybridisation, expression was found in the cell bodies of about 40 % of preganglionic sympathetic neurons and was observed at all levels from T3 to S2 (Ferens et al 2010a).…”

The Effects of Some Neuropeptides on Motor Activity of Smooth Muscle Organs in Abdominal and Pelvic Cavities

“…They are also expressed by lumbosacral autonomic preganglionic neurons of the micturition reflex pathways (Ferens et al, 2010) The activation of the receptor causes the stimulation of the G-protein subunit Gα11. This leads to the activation of intracellular signaling cascades via the phospholipase C (PLC) (Vartiainen, 2009).…”