title: Stimulation of dopamine D2-like receptors in the lumbosacral defaecation centre causes propulsive colorectal contractions in rats.
abstract: The pathophysiological roles of the CNS in bowel dysfunction in patients with irritable bowel syndrome and Parkinson's disease remain obscure. In the present study, we demonstrate that dopamine in the lumbosacral defaecation centre causes strong propulsive motility of the colorectum. The effect of dopamine is a result of activation of sacral parasympathetic preganglionic neurons via D2-like dopamine receptors. Considering that dopamine is a neurotransmitter of descending pain inhibitory pathways, our results highlight the novel concept that descending pain inhibitory pathways control not only pain, but also the defaecation reflex. In addition, severe constipation in patients with Parkinson's disease can be explained by reduced parasympathetic outflow as a result of a loss of the effect of dopaminergic neurons.
  
  
  
  We have recently demonstrated that intrathecally injected noradrenaline caused propulsive contractions of the colorectum. We hypothesized that descending pain inhibitory pathways control not only pain, but also the defaecation reflex. Because dopamine is one of the major neurotransmitters of descending pain inhibitory pathways in the spinal cord, we examined the effects of the intrathecal application of dopamine to the spinal defaecation centre on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anaesthetized rats. Slice patch clamp and immunohistochemistry were used to confirm the existence of dopamine-sensitive neurons in the sacral parasympathetic nuclei. Intrathecal application of dopamine into the L6-S1 spinal cord, where the lumbosacral defaecation centre is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons using TTX blocked the effect of dopamine. Although thoracic spinal transection had no effect on the enhancement of colorectal motility by intrathecal dopamine, the severing of the pelvic nerves abolished the enhanced motility. Pharmacological experiments revealed that the effect of dopamine is mediated primarily by D2-like dopamine receptors. Neurons labelled with retrograde dye injected at the colorectum showed an inward current in response to dopamine in slice patch clamp recordings. Furthermore, immunohistochemical analysis revealed that neurons immunoreactive to choline acetyltransferase express D2-like dopamine receptors. Taken together, our findings demonstrate that dopamine activates sacral parasympathetic preganglionic neurons via D2-like dopamine receptors and causes propulsive motility of the colorectum in rats. The present study supports the hypothesis that descending pain inhibitory pathways regulate defaecation reflexes.
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Kiyotada
authors.initials: K
authors.lastname: Naitou
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamori
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shiina
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Yuuta
authors.initials: Y
authors.lastname: Nozue
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, Morioka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, Morioka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Akimoto
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.affiliation: Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Shimizu
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003672:Defecation / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D007278:Injections, Spinal; D008161:Lumbosacral Region / Q000294:innervation / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D012007:Rectum / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology / Q000601:surgery; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D001552:Benzazepines; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D019257:Quinpirole; D013779:Tetrodotoxin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol; D004298:Dopamine