Book of Abstracts - Australian Centre for Economic Research on ...

3rd Cell Stress Society International Congress on
Stress Responses in Biology and Medicine and
2nd World Conference <strong>of</strong> Stress
6I. MODERN MOLECULAR MECHANISMS AND THERAPEUTICS
OF STRESS-RELATED GASTROINESTINAL DISORDERS
(SÁNDOR SZABÓ, YVETTE TACHÉ)
6I_01_S
STRESS AND THE GUT: ROLE OF CORTICOTROPIN RELEASING FACTOR (CRF)
SIGNALING PATHWAYS
Y. Taché
Center <strong>for</strong> Neurovisceral Sciences, Department <strong>of</strong> Medicine, University <strong>of</strong> Cali<strong>for</strong>nia, Los Angeles, USA
The characterization and distribution <strong>of</strong> corticotropin-releasing factor (CRF) family <strong>of</strong> peptides, CRF,
urocortin 1, urocortin 2 and urocortin 3, and the two G-protein coupled receptors, CRF 1 and CRF 2 , as well
as the development <strong>of</strong> selective CRF 1 and CRF 2 receptor antagonists provided novel means to understand
mechanisms involve in the stress response. The activation <strong>of</strong> brain CRF 1 signaling pathway plays a primary
role in the endocrine (activation <strong>of</strong> pituitary adrenal axis), behavioral (anxiety, depression), autonomic
(sympathetic activation), and decrease immune responses to stress. Combined anatomical, pharmacologic and
molecular approaches support a role <strong>of</strong> CRF receptor activation in both the brain and the gut as part <strong>of</strong> key
mechanisms involved in stress-related alterations <strong>of</strong> gut propulsive function. Inhibition <strong>of</strong> gastric emptying
and stimulation <strong>of</strong> colonic motor function are the commonly encountered patterns resulting from exposure
to various stressors in experimental animals and humans. Activation <strong>of</strong> brain and peripheral CRF 2 receptors
mediates stress-related inhibition gastric motor function while that <strong>of</strong> CRF 1 receptors are involved in the
stimulation colonic secretory and motor functions. Clinical investigations also support the notion that stress
contributes to visceral hypersensitivity <strong>of</strong> the gut observed in patients with irritable bowel syndrome (IBS) as
established by their lowered threshold <strong>of</strong> pain to colorectal distension (CRD). Experimental models have
been developed that recapture clinical features <strong>of</strong> IBS with regard to stress-related hyperalgesia to CRD,
gender differences, comorbidity with anxiety/depression and altered bowel habit. Data obtained using
pharmacologic approaches in rodents subjected to stress indicate that the activation <strong>of</strong> CRF 1 receptor
contributes to the development <strong>of</strong> hyperalgesia to CRD while CRF 2 receptors display opposite effects. The
mechanisms through which CRF 1 antagonists alleviate colonic responses involved the prevention <strong>of</strong> stressrelated
activation <strong>of</strong> sacral parasympathetic ouflow, colonic enteric cholinergic neurons and mast cells. The
pre-clinical and clinical phase I data support that targeting <strong>of</strong> CRF 1 receptors may open new therapeutic
venues <strong>for</strong> stress-related functional gastrointestinal disorders. Supported by NIHDDK and VA Merit grants.
6I_02_S
EFFECT OF CAPSAICIN ON THE ESOPHAGEAL MOTILITY OF PATIENTS WITH
GASTRO-ESOPHAGEAL REFLUX DISEASE (GERD)
Agnes Király
3rd Dept. <strong>of</strong> Medicine, University <strong>of</strong> Pécs, Hungary
e-mail: agnes.kiraly@aok.pte.hu
Capsaicin-sensitive afferents play a role in the regulation <strong>of</strong> esophageal motility. Vanilloid receptor is activated
by acidic pH which triggers pain and motor responses leading to esophageal emptying . The aim was to
investigate the effect <strong>of</strong> topical capsaicin (Tabasco) suspension on esophageal sensation and motility in
healthy controls (N=10), patients with non-erosive GERD (NERD) (N=10), erosive esophagitis (ERD)
371