Role of brain kallikrein-kinin system in regulation of adrenocorticotropin release

We evaluated whether the brain kallikrein-kinin system plays a role in the regulation of adrenocorticotropin (ACTH) release in rats. Intracerebroventricular (icv) injection of bradykinin (0.24 nmol) increased plasma immunoreactive ACTH (irACTH) levels (from 93 ± 4 to 200 ± 12 pg/ml, P <0.01). This effect was prevented by icv kinin antagonist at 15.4 nmol/h (from 98 ± 5 to 108 ± 6 pg/ml; not significant). The antagonist did not alter the increase in plasma irACTH levels induced by icv corticotropin- releasing factor (CRF), arginine vasopressin, or prostaglandin E₂. Melittin (7 nmol/h icv) increased plasma irACTH from 95 ± 4 to 268 ± 7 pg/ml (P <0.01). This effect was prevented by icv kinin antagonist (15.4 nmol/h), kallikrein antibodies (13 pmol/h), or indomethacin (0.28 mmol/h). ACTH response to melittin was not altered by antagonists of CRF or vasopressin. Intra-arterial injection of insulin (0.3 IU/kg body wt) reduced plasma glucose levels to a similar extent in rats given icv kinin antagonist or vehicle; the ACTH response to insulin-induced hypoglycemia was slightly less in rats given kinin antagonist than in those given vehicle (55 ± 5 vs. 86 ± 4 pg/ml, P <0.05). The brain kallikrein-kinin system may play a role in the regulation of ACTH secretion in stimulated conditions.