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Can modulating corticotropin releasing hormone receptors alter visceral sensitivity?
  1. S Fukudo1,
  2. K Saito1,
  3. Y Sagami2,
  4. M Kanazawa1
  1. 1Department of Behavioural Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2Department of Psychosomatic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  1. Correspondence to:
    Professor S Fukudo
    Department of Behavioural Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; sfukudo{at}mail.tains.tohoku.ac.jp

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Activation of corticotropin releasing hormone (CRH) receptor 2 (CRH-R2) reduces visceral sensitivity induced by colorectal distension in conscious rats. This finding is relevant to the increased interest in the potential use of therapeutic agents that act on CRH receptors in the treatment of irritable bowel syndrome

Clarifying the adverse effects of stress on bodily function is a crucial paradigm for medical research. Evidence that psychosocial stress aggravates digestive diseases has been accumulating and stress induced exacerbation of symptoms in patients with functional gastrointestinal disorders is well recognised.1 Corticotropin releasing hormone (CRH), a 41 amino acids peptide produced mainly in the paraventricular nucleus of the hypothalamus, is considered to be a major mediator of the stress response.2 Indeed, stress is known to induce release of hypothalamic CRH, resulting in pituitary secretion of adrenocorticotropic hormone (ACTH). In addition, stress related activation of CRH receptors has been reported to alter gastrointestinal functions.3 Moreover, physical or psychological stress is known to delay gastric emptying,4 accelerate colonic transit,5 and evoke colonic motility6 in rats.

Two major G protein coupled receptors for the CRH have been identified, CRH receptor 1 (CRH-R1) and receptor 2 (CRH-R2).7–9 CRH-R1, which is highly expressed in the anterior pituitary, neocortex, hypothalamus, hippocampus, amygdala, locus coeruleus, and cerebellum, has been reported to mediate stress induced physiological changes, including stimulation of the hypothalamo-pituitary-adrenal axis, elevation of plasma levels of catecholamines, increased colonic motility,10 and exaggerated stress related behaviour, especially anxiety.11,12 In addition, stimulation of this receptor is believed to activate adenylate cyclase, an enzyme that catalyses the formation of cyclic AMP (cAMP).7–9

We have previously reported increased colonic motility and visceral perception in response to administration of CRH in patients with irritable bowel syndrome (IBS).13 In addition, earlier …

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