Effects of tricyclic antidepressants on mechanosensitive pelvic nerve afferent fibers innervating the rat colon. 1998

X Su, and G F Gebhart
The University of Iowa, College of Medicine, Department of Pharmacology, Iowa City 52242, USA. xin-su@uiowa.edu

The aim of this study was to examine the effects of tricyclic antidepressants on responses of mechanosensitive afferent fibers innervating the rat colon. A total of 53 fibers in the decentralized S1 dorsal root were studied. The effects of the non-specific monoamine reuptake inhibitor imipramine (IMI), the noradrenaline reuptake inhibitor desipramine (DES), and the serotonin reuptake inhibitor clomipramine (CLO) were tested on responses of 22 mechanosensitive afferent fibers to noxious colorectal distension (CRD; 80 mmHg). Cumulative doses of 16 mg/kg of IMI, DES and of CLO reduced responses to noxious CRD to a mean 20%, 22% and 46% of control, respectively. The mean inhibitory doses of the three antidepressants did not differ significantly. Inhibitory effects were independent of potential effects on neurotransmitter reuptake: the effects of IMI and DES were not blocked by the adrenoreceptor antagonist phentolamine, and the effects of IMI and CLO were not affected by the serotonin receptor antagonist metergoline. Attenuation of afferent nerve activity was not mimicked by the anticholinergic glycopyrrolate; the cholinesterase inhibitor neostigmine did not attenuate the effect of IMI on responses to noxious CRD. Interestingly, the opioid receptor antagonist naloxone partially reversed the effects of IMI, and the NMDA receptor channel blocker MK-801 enhanced the inhibitory effects of DES and CLO. These results document that responses of mechanosensitive pelvic nerve afferent fibers to noxious CRD are significantly attenuated by tricyclic antidepressants, a peripheral action that may contribute to the beneficial effects of tricyclic antidepressants in treatment of irritable bowel syndrome.

UI MeSH Term Description Entries
D008297 Male Males
D008465 Mechanoreceptors Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures. Golgi Tendon Organ,Golgi Tendon Organs,Krause's End Bulb,Krause's End Bulbs,Mechanoreceptor,Mechanoreceptor Cell,Meissner's Corpuscle,Neurotendinous Spindle,Neurotendinous Spindles,Receptors, Stretch,Ruffini's Corpuscle,Ruffini's Corpuscles,Stretch Receptor,Stretch Receptors,Mechanoreceptor Cells,Bulb, Krause's End,Bulbs, Krause's End,Cell, Mechanoreceptor,Cells, Mechanoreceptor,Corpuscle, Meissner's,Corpuscle, Ruffini's,Corpuscles, Ruffini's,End Bulb, Krause's,End Bulbs, Krause's,Krause End Bulb,Krause End Bulbs,Krauses End Bulb,Krauses End Bulbs,Meissner Corpuscle,Meissners Corpuscle,Organ, Golgi Tendon,Organs, Golgi Tendon,Receptor, Stretch,Ruffini Corpuscle,Ruffini Corpuscles,Ruffinis Corpuscle,Ruffinis Corpuscles,Spindle, Neurotendinous,Spindles, Neurotendinous,Tendon Organ, Golgi,Tendon Organs, Golgi
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009270 Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. MRZ 2593-Br,MRZ-2593,Nalone,Naloxon Curamed,Naloxon-Ratiopharm,Naloxone Abello,Naloxone Hydrobromide,Naloxone Hydrochloride,Naloxone Hydrochloride Dihydride,Naloxone Hydrochloride, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Naloxone, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Narcan,Narcanti,Abello, Naloxone,Curamed, Naloxon,Dihydride, Naloxone Hydrochloride,Hydrobromide, Naloxone,Hydrochloride Dihydride, Naloxone,Hydrochloride, Naloxone,MRZ 2593,MRZ 2593 Br,MRZ 2593Br,MRZ2593,Naloxon Ratiopharm
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D010388 Pelvis The space or compartment surrounded by the pelvic girdle (bony pelvis). It is subdivided into the greater pelvis and LESSER PELVIS. The pelvic girdle is formed by the PELVIC BONES and SACRUM. Pelvic Region,Region, Pelvic
D010525 Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Endoneurium,Epineurium,Perineurium,Endoneuriums,Epineuriums,Nerve, Peripheral,Nerves, Peripheral,Perineuriums,Peripheral Nerve
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental

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