Abstract
The central nervous system is involved in regulation of defaecation. It is generally considered that supraspinal regions control the spinal defaecation centre. However, signal transmission from supraspinal regions to the spinal defaecation centre is still unclear. In this study, we investigated the regulatory role of an anorexigenic neuropeptide, α-MSH, in the spinal defaecation centre in rats. Intrathecal administration of α-MSH to the L6-S1 spinal cord enhanced colorectal motility. The prokinetic effect of α-MSH was abolished by severing the pelvic nerves. In contrast, severing the colonic nerves or thoracic cord transection at the T4 level had no impact on the effect of α-MSH. RT-PCR analysis revealed MC1R mRNA and MC4R mRNA expression in the L6-S1 spinal cord. Intrathecally administered MC1R agonists, BMS470539 and SHU9119, mimicked the α-MSH effect, but a MC4R agonist, THIQ, had no effect. These results demonstrate that α-MSH binds to MC1R in the spinal defaecation centre and activates pelvic nerves, leading to enhancement of colorectal motility. This is, to our knowledge, the first report showing the functional role of α-MSH in the spinal cord. In conclusion, our findings suggest that α-MSH is a candidate for a neurotransmitter from supraspinal regions to the spinal defaecation centre.
Highlights
Defaecation is regulated by the enteric nervous system in the periphery and by the central nervous system
We focused on the action of α-melanocyte-stimulating hormone (α-MSH) in the spinal defaecation centre. α-MSH is an anorexigenic neuropeptide derived from the precursor polypeptide proopiomelanocortin (POMC) and it binds to melanocortin receptors (MCR) subtypes 1, 3, 4 and 515
Our major findings are (1) α-MSH administered to the spinal cord at the L6-S1 level caused propulsive contractions of the colorectum in anaesthetised rats with ketamine and α-chloralose, (2) severing the pelvic nerves, but not severing the lumbar colonic nerves or T4 thoracic transection, abolished the effect of intrathecally administered α-MSH, (3) melanocortin-1 receptor (MC1R) mRNA and MC4R mRNA were expressed in the spinal cord at the L6-S1 level, and (4) intrathecally administered MC1R, but not MC4R, agonists enhanced colorectal motility
Summary
Defaecation is regulated by the enteric nervous system in the periphery and by the central nervous system. It has been shown that ghrelin receptors are expressed in the spinal defaecation centre and that activation of the receptors enhances colorectal motility by activating preganglionic neurons of the sacral parasympathetic nuclei innervating the colorectum[13,14]. Owing to the fact that α-MSH has the opposite effect to that of ghrelin in the hypothalamus, we assumed that α-MSH exerts the opposite effect to the prokinetic action of ghrelin on colorectal motility in the spinal defaecation centre. To verify this hypothesis, we examined the effects of α-MSH administration into the L6-S1 spinal cord, where the defaecation centre is located, in anaesthetised rats. In this study, we performed further investigation into the mechanisms of α-MSH-induced enhancement of colorectal motility
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