alpha-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion

作者：Huang Hsien Hao; Chen Liang Yu; Doong Ming Luen; Chang Shi Chuan; Chen Chih Yen^*

来源：Drug Design, Development and Therapy, 2017, 11: 2377-2386.

DOI：10.2147/DDDT.S143749

• acyl ghrelin
• colon transit time
• fecal pellet output
• food intake
• gastric emptying
• intracerebroventricular
• small intestinal transit
• alpha-melanocyte stimulating hormone

Background: Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of alpha-melanocyte stimulating hormone (alpha-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect.
Objective: This study aimed to investigate the modulating effect of alpha-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats.
Methods and procedures: We examined the effects of alpha-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters.
Results: ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P<0.01), enhanced non-nutrient semi-liquid gastric emptying (P<0.001), increased the geometric center and running percentage of small intestinal transit (P<0.001), accelerated colonic transit time (P<0.05), and increased fecal pellet output (P<0.01) and total fecal weight (P<0.01). Pretreatment with ICV injection of alpha-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of alpha-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit (P<0.01). However, neither dose of alpha-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time.
Conclusion: alpha-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. alpha-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.

• 出版日期2017