Abstract
Acupuncture at homotopic acupoints or heterotopic acupoints is known to either inhibit or facilitate gastrointestinal motility, depending on the acupoint location. However, little effort has been made to investigate the roles of specific receptors (such as adrenergic and muscarinic acetylcholine receptors) in mediating the effects of acupuncture at heterotopic and homotopic acupoints. Different adrenergic receptor subtypes or cholinergic receptor subtypes are predominantly expressed in various sections of the gut, resulting in variations between the effects of acupuncture at heterotopic or homotopic acupoints on gastrointestinal motility. Here, we investigated the role of β1/β2 receptors and M2/M3 receptors in gastrointestinal motility regulated by acupuncture at ST37, a heterotopic acupoint, and ST25, a homotopic acupoint, by simultaneously recording intraluminal pressures in the distal colon and stomach or jejunum and examining fecal phenol red excretion in β1/2 receptor-knockout mice and M2/3 receptor-knockout mice. We found that knockout of the M2/3 receptor significantly inhibited ST37 acupuncture-induced enhancement of gastric motility, jejunal motility, and colonic motility. Additionally, knocking out of the β1/2 receptor significantly diminished the ST25 acupuncture-induced inhibition of gastric motility and jejunal motility without significantly altering the enhancement of colonic motility induced by acupuncture at ST25. Acupuncture at ST37 significantly accelerated gastrointestinal transition in β1/2 receptor-knockout mice and their wild-type littermates. However, this acceleration of gastrointestinal transition was markedly diminished in M2/3 receptor-knockout mice relative to their wild-type littermates. Acupuncture at ST25 significantly increased gastrointestinal transition in β1/2 receptor-knockout mice and significantly decreased gastrointestinal transition in M2/3 receptor-knockout mice without altering gastrointestinal transition in wild-type littermates of either. Our study revealed that M2/3 receptors are required for the gastrointestinal motility associated with whole gastrointestinal transition enhanced by acupuncture at heterotopic acupoints, whereas β1/2 receptors are required for the same gastrointestinal motility processes inhibited by acupuncture at homotopic acupoints. Therefore, our findings reveal important biological mechanisms underlying acupuncture treatment of disorders involving gastrointestinal motility dysfunction.
Highlights
The efficacy of acupuncture-like somatic stimulation on the treatment of gastrointestinal motility disorders has been established in both clinical and research settings [1,2,3,4,5,6,7]
We found that acupuncture at ST37 could enhance gastrointestinal motility involved in whole gastrointestinal transition via activating M2/3 receptors; whereas acupuncture at ST25 could slow down a majority of gastrointestinal motility through activating β1/2 receptors
We investigated the phenotypic and functional differences in the pylorus, jejunum, and distal colon between M2/3 KO mice, β1/2 KO mice, and their wild-type littermates at basal conditions and in response to manual acupuncture stimulation at the acupoints ST37 and ST25
Summary
The efficacy of acupuncture-like somatic stimulation on the treatment of gastrointestinal motility disorders has been established in both clinical and research settings [1,2,3,4,5,6,7]. Acupuncture at heterotopic acupoints, involving different segmental innervation of the spinal cord to visceral organs, induces gastrointestinal facilitation only in complete spinal rats [9]. Little effort has been made far to investigate the roles of specific ligand receptors (such as adrenergic and muscarinic acetylcholine receptors) in mediating the effects of acupuncture, at heterotopic or homotopic acupoints, on motility of various sections of gut. Β-AR stimulation has been shown to consistently produce a relaxation response in a range of human gastrointestinal smooth muscle preparations. The range of muscle relaxation responses in the ileum, colon, and rectum, following βAR agonism by various pharmacological agents, suggests differing roles for β-ARs in longitudinal and circular smooth muscle cell types [10]. The range of muscle relaxation responses in the ileum, colon, and rectum, following βAR agonism by various pharmacological agents, suggests differing roles for β-ARs in longitudinal and circular smooth muscle cell types [10]. β1-and β2-ARs may have roles in gastrointestinal motility that are regulated by the sympathetic nervous system [11]
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