Vasoactive intestinal polypeptide stimulates the secretion of catecholamines from the rat adrenal gland.

1. Our previous studies have indicated that splanchnic nerves release a substance(s), other than acetylcholine, that induces the secretion of catecholamines from the rat adrenal medulla. To identify the nature of the non-cholinergic substance, the effects of met-enkephalin and vasoactive intestinal polypeptide (VIP) were investigated in the perfused adrenal gland of the rat. 2. The secretion of catecholamines increased from a basal level of 8 ng to a maximum value of 18 ng during perfusion with 100 microM-met-enkephalin. The secretion evoked by 10 micrograms acetylcholine increased from 118 to 143 ng in the presence of 10 microM-met-enkephalin. Higher concentrations of met-enkephalin (100 microM) had no additional effect. Secretion of catecholamines evoked by stimulation of splanchnic nerves (10 Hz for 30 s) was even less (8%) affected by met-enkephalin. 3. 0.3 microM-VIP caused a significant increase in the secretion of catecholamines, and the effect increased with an increase in the concentration of VIP. About 115 ng of catecholamines were secreted during 15 min perfusion with 3 microM-VIP. 4. VIP-evoked secretion was not affected by antagonists of nicotinic and muscarinic receptors, nor by chronic splanchnicotomy. However, removal of calcium ions from, and inclusion of 1 mM-EGTA in, the perfusion medium completely inhibited the secretion evoked by VIP. 5. VIP-evoked secretion was reduced (20-75%) in a concentration-dependent manner by 3-30 microM-naloxone. 6. It is suggested that VIP may be the non-cholinergic excitatory substance present in the splanchnic nerves and released along with acetylcholine during simulation of the nerves to evoke secretion of catecholamine from the rat chromaffin cells.