The peptide VIP is a neurotransmitter in rat adrenal medulla: physiological role in controlling catecholamine secretion.

1. The perfused adrenal gland of the rat was used to establish the identity of a non-cholinergic substance involved in splanchnic nerve-mediated secretion of catecholamines. 2. The perfused adrenal medulla was rich in vasoactive intestinal polypeptide (VIP) content (28 pmol g-1 of wet tissue). VIP-immunoreactive nerve fibres were present in the adrenal medulla and the adrenal cortex. 3. Field stimulation (10 Hz for 15 min plus 1 Hz for 15 min) caused a large increase in the output of VIP in the perfusate over the spontaneous release of VIP. Secretion of catecholamines was also greatly elevated by field stimulation. Field stimulation-evoked output of VIP and catecholamines was abolished after chronic denervation of the adrenal glands. 4. Infusion of acetylcholine (ACh) did not increase the output of VIP but caused a robust secretion of catecholamines. 5. The VIP output declined when the stimulation frequency was increased (8.6 x 10(-3) fmol pulse-1 at 1 Hz and 4.0 x 10(-3) fmol pulse-1 at 10 Hz). 6. In contrast, the output of 3H-acetylcholine (3H-ACh, expressed as a fraction of tissue 3H-ACh content) increased from 7.0 x 10(-2) pulse-1 at 1 Hz to 16.3 x 10(-2) pulse-1 at 10 Hz. 7. Secretion of catecholamines evoked by low-frequency stimulation (1 Hz) was reduced by 40% in the presence of cholinergic receptor antagonists (atropine plus hexamethonium). Inclusion of a VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) caused about 75% inhibition. 8. The VIP receptor antagonist inhibited VIP-evoked secretion of catecholamines without affecting ACh-evoked secretion. 9. In conclusion, VIP satisfies all the essential criteria to assume the role of a neurotransmitter in the rat adrenal medulla. The contribution of VIP to the secretion of adrenal medullary hormones is more prominent at low rates of neuronal activity whereas ACh is the major contributor at higher activity.