INTRACEREBROVENTRICULARLY ADMINISTERED CORTICOTROPIN-RELEASING FACTORRELEASES SOMATOSTATIN THROUGH A CHOLINERGIC, VAGAL PATHWAY IN FREELY FEED RATS

The aim of this study was to investigate whether corticotropin-releasi ng factor influences the plasma levels of somatostatin, gastrin or cho lecystokinin when administered intracerebroventricularly to rats, and if such an effect could be vagally mediated, and dependent on the anim als feeding states. Anaesthetized, freely fed rats were given 5 mu l i ntracerebroventricular injections of corticotropin-releasing factor in four doses; 10 pmol-1.28 nmol. Immediately following death, trunk blo od was collected for subsequent peptide analysis with radioimmunoassay (RIA). The three higher doses of corticotropin-releasing factor eleva ted the plasma levels of somatostatin (P < 0.01) after 20 min but left the plasma levels of gastrin and cholecystokinin unchanged. Intraperi toneal injections of 60 and 320 pmol of corticotropin-releasing factor did not influence the somatostatin levels. Further, intracerebroventr icular injections of 60 pmol of corticotropin-releasing factor produce d a peak increase in somatostatin after 20 min (P < 0.01). After 60 mi n the somatostatin levels were still increased (P < 0.05). Gastrin and cholecystokinin remained unaltered at these timepoints. Intracerebrov entricular administration of 10 nmol of alpha-helical corticotropin-re leasing factor 9-41 attenuated the basal levels of somatostatin and bl ocked the corticotropin-releasing factor-induced rise in somatostatin. Bilateral truncal vagotomy, as well as pretreatment with atropine (0. 05 mg kg(-1), subcutaneously) abolished the effects of corticotropin-r eleasing factor on somatostatin. In animals which were food-deprived f or 24 h, corticotropin-releasing factor did not influence somatostatin , gastrin or cholecystokinin. Pretreatment with cholecystokinin did no t potentiate corticotropin-releasing factor-induced somatostatin relea se in food-deprived rats. These findings suggest that corticotropin-re leasing factor acting within the central nervous system may regulate g astrointestinal functions partially through a cholinergic, vagally med iated release of somatostatin in freely fed, but not in food-deprived rats.