β1/2 or M2/3 Receptors Are Required for Different Gastrointestinal Motility Responses Induced by Acupuncture at Heterotopic or Homotopic Acupoints

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.

Effect of Electroacupuncture at Zusanli (ST36) on Sepsis Induced by Cecal Ligation Puncture and Its Relevance to Spleen

“…By summarizing data from existing researches, Yu [ 45 ] put forward that stimulating acupoints located at arms and legs, such as ST36 and LI11, activates vagal efferent fiber and results in positive gut motility, and stimulating acupoints distributed in the abdomen (like ST25) regulates gut motility negatively in a sympathetic dependent way. Vagotomy or knockout genes encoding M2 and M3 receptors can reduce the former action and antagonist of sympathetic nerve or deletion of genes encoding β 1 and β 2 receptors can attenuate the latter effect [ 42 – 44 , 46 ]. These results indicated that we can choose different acupoints for EA depending on different kinds of gastrointestinal dysfunction.…”

Neuromechanism of acupuncture regulating gastrointestinal motility

“…The β1 and β2 receptors are expressed in the GI tract and serve as the predominant subtypes in the inhibitory effects of the SNS on GI motility[ 47 , 48 ], while the M2 and M3 receptors serve as the predominant subtypes in the excitatory effects of the PNS on GI motility[ 49 , 50 ]. The effect of acupuncture on GI motility could also be reduced by the corresponding antagonist[ 51 - 54 ] and deletion of the gene encoding the β 1&2 receptor or M 2&3 receptor[ 55 - 57 ]. In addition to the excitement effect, lower extremity acupoints also suggest an inhibitory effect on GI movement, and the inhibitory rate of ST37/LI11 on gastric movement fluctuates between 6.67%–1.33%[ 58 , 59 ].…”

Choosing an Animal Model for the Study of Functional Dyspepsia

“…The effects of acetylcholine on gastrointestinal contractility are mainly regulated by muscarinic acetylcholine receptors [ 62 ]. So the activity of muscarinic acetylcholine receptors is directly tied to the gastrointestinal motility [ 63 ]. Atropine, a muscarinic acetylcholine receptor antagonist, could be used to induce delay in gastrointestinal transit [ 10 ].…”