EVIDENCE FOR CENTRAL NERVOUS EFFECTS OF CORTICOTROPIN-RELEASING HORMONE ON GASTRIC-ACID SECRETION IN HUMANS

In animals, corticotropin-releasing hormone (CRH) has been shown to de crease gastric acid secretion after intracerebral administration. Evid ence exists that in man peptides have a direct access to the brain upo n intranasal administration. This study aimed at assessing brain-media ted effects of CRH on gastric pH after intranasal administration in hu mans. Eleven healthy men were tested on 2 occasions in a double-blind within-subject cross-over comparison during treatment with CRH (versus placebo) administered intranasally at a dose of 20 mu g every 10 min. Gastric pH values were measured continuously by a gastral pH tube. Af ter 2 h of intranasal treatment, 6 mu g/kg pentagastrin was injected s ubcutaneously. The subject's mood was assessed by an adjective list (E WL-N) at the end of each experimental condition. Intranasal CRH increa sed pH baseline values from (mean +/- SE) 1.70 +/- 0.31 to 2.62 +/- 0. 53 (corresponding to 54%), whereas during intranasal treatment with pl acebo pH values remained unchanged (p < 0.05). After injection of pent agastrin, pH values decreased to 0.73 +/- 0.04 during placebo and to 0 .93 +/- 0.14 during CRH treatment (n.s.). During treatment with CRH, s ubjects felt less tired (p < 0.05) and deactivated (p < 0.05). Plasma cortisol and CRH levels were not affected by intranasal CRH, excluding mediation of the CRH effects via resorption into the bloodstream, and TSH levels were slightly decreased by the end of the treatment. Resul ts confirm the notion of a pathway for CRH from the nose to the brain, initiating, via central nervous mechanisms, inhibition of gastric aci d secretion and a change of mood in humans.