Intracerebroventricularly administered corticotropin-releasing factor releases somatostatin through a cholinergic, vagal pathway in freely fed rats.
The aim of this study was to investigate whether corticotropin-releasing factor influences the plasma levels of somatostatin, gastrin or cholecystokinin when administered intracerebroventricularly to rats, and if such an effect could be vagally mediated, and dependent on the animals feeding states. Anaesthetized, freely fed rats were given 5 microliters intracerebroventricular injections of corticotropin-releasing factor in four doses; 10 pmol-1.28 nmol. Immediately following death, trunk blood was collected for subsequent peptide analysis with radioimmunoassay (RIA). The three higher doses of corticotropin-releasing factor elevated the plasma levels of somatostatin (P < 0.01) after 20 min but left the plasma levels of gastrin and cholecystokinin unchanged. Intraperitoneal injections of 60 and 320 pmol of corticotropin-releasing factor did not influence the somatostatin levels. Further, intracerebroventricular injections of 60 pmol of corticotropin-releasing factor produced a peak increase in somatostatin after 20 min (P < 0.01). After 60 min the somatostatin levels were still increased (P < 0.05). Gastrin and cholecystokinin remained unaltered at these time-points. Intracerebroventricular administration of 10 nmol of alpha-helical corticotropin-releasing factor 9-41 attenuated the basal levels of somatostatin and blocked 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-releasing factor on somatostatin. In animals which were food-deprived for 24 h, corticotropin-releasing factor did not influence somatostatin, gastrin or cholecystokinin. Pretreatment with cholecystokinin did not potentiate corticotropin-releasing factor-induced somatostatin release in food-deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Smedh
U
U
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Uvnäs-Moberg
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017776:Autonomic Pathways / Q000502:physiology*; D002766:Cholecystokinin / Q000097:blood / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005260:Female; D005508:Food Deprivation; D005755:Gastrins / Q000097:blood; D007276:Injections, Intraventricular; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000097:blood*; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D005755:Gastrins; D013004:Somatostatin; D001285:Atropine; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone