MICROINFUSION OF CORTICOTROPIN-RELEASING FACTOR INTO THE LOCUS-COERULEUS SUBCOERULEUS NUCLEI INHIBITS GASTRIC-ACID SECRETION VIA SPINAL PATHWAYS IN THE RAT

Brain corticotropin-releasing factor (CRF) is involved in stress-relat ed alterations of gastric acid secretion. CRF in the locus coeruleus h as been shown to induce anxiogenic behavioral responses and to mimic s tress-induced alterations of colonic motor function. Whether the locus coeruleus/subcoeruleus nucleus (LC/SC) is a site of action for CW to alter gastric acid secretion was investigated in urethane-anesthetized gastric fistula rats. In sham-operated animals, CRF (126-420 pmol) mi croinfused bilaterally into the LC/SC induced a dose-dependent inhibit ion of pentagastrin (PG)-stimulated gastric acid secretion of 60-81% w ithin the first hour after microinjection. At the 420 pmol dose, this inhibitory effect of CRF into the LC/SC lasted throughout the whole ob servation period of 120 min. After bilateral vagotomy, basal and PG-st imulated gastric acid secretion at microinjection of vehicle was reduc ed. Nevertheless, microinfusion of 420 pmol CRF into the LC/SC still i nhibited significantly gastric acid secretion by 62.1%. In contrast, i n spinal cord transected animals bilateral microinfusion of 420 pmol C RF into the LC/SC did not reduce PG-stimulated gastric acid secretion. These data indicate that CRF acts in the LC/SC to induce a long lasti ng inhibition of peripherally stimulated gastric acid secretion via sp inal pathways. These findings suggest a possible role of the LC/SC in the regulation of gastric secretion and of endogenous CRF at these sit es in the stress-related inhibition of gastric acid secretion by affec ting autonomic nervous system activity.