Water avoidance stress induces visceral hyposensitivity through peripheral corticotropin releasing factor receptor type 2 and central dopamine D2 receptor in rats.

BACKGROUND: Water avoidance stress (WAS) is reported to induce functional changes in visceral sensory function in rodents, but the results which have been demonstrated so far are not consistent, i.e., hypersensitivity or hyposensitivity. We determined the effect of WAS on visceral sensation and evaluated the mechanisms of the action. METHODS: Visceral sensation was assessed by abdominal muscle contractions induced by colonic balloon distention, i.e., visceromotor response (VMR), measured electrophysiologically in conscious rats. The electromyogram electrodes were acutely implanted under anesthesia on the day of the experiment. The threshold of VMR was measured before and after WAS for 1 h. To explore the mechanisms of WAS-induced response, drugs were administered 10 min prior to the initiation of WAS. KEY RESULTS: WAS significantly increased the threshold of VMR, and this effect was no longer detected at 24 h after. Intraperitoneal injection of astressin2 -B (200 µg/kg), a corticotropin releasing factor (CRF) receptor type 2 antagonist abolished the response by WAS. Subcutaneous (sc) injection of sulpiride (200 mg/kg), a dopamine D2 receptor antagonist blocked the response, while sc domperidone (10 mg/kg), a peripheral dopamine D2 receptor antagonist did not alter it. Naloxone (1 mg/kg, sc), an opioid antagonist did not modify it either. CONCLUSIONS & INFERENCES: WAS induced visceral hyposensitivity through peripheral CRF receptor type 2 and central dopamine D2 receptor, but not through opioid pathways. As altered pain inhibitory system was reported to be observed in the patients with irritable bowel syndrome, CRF and dopamine signaling might contribute to the pathophysiology.

Effect of NaCl on Aggregation Number, Microviscosity, and Cmc of N-Dodecanoyl Amino Acid Surfactant Micelles

Microviscosity, micellar aggregation number (N), and critical micelle concentration (cmc) were determined in solutions of sodium N-dodecanoyl-glycinate (Lau-Gly), -valinate (Lau-Val), -leucinate (Lau-Leu), and -phenylalaninate (Lau-Phe) as a function of NaCl using fluorescent probes (auramine, pyrene). The microviscosity increased with increasing concentration of NaCl and reached a saturated value. In addition, two breakpoints were found on the curve of microviscosity vs NaCl concentration and by comparison with the data of N and solution viscosity. The first and second breakpoints were explained, respectively, as the beginnings of micellar growth and intermicellar interaction. The value of N increased steeply above the first breakpoint and the solution viscosity began to increase at the second breakpoint. The NaCl concentrations at the first and second breakpoints increased in the order Lau-Phe < Lau-Leu < Lau-Val approximately Lau-Gly. The absolute value of the slope of the Corrin-Harkins plot of the cmc was smaller for Lau-Leu and -Phe than for Lau-Gly and -Val. Larger absolute values of the slope (1.2 approximately 2), which suggested the contribution of a salting out effect on cmc, were observed at high NaCl concentration for Lau-Gly and -Val. The micellar growth and intermicellar interaction occurred at lower NaCl concentration with increased size of the amino acid residue when the amino acid of the amino acid surfactant was larger than valine; that is, the hydrophobicity of the amino acid residue was the dominant factor rather than steric hindrance.