Importance of Cholinergic and Peptidergic Transmitters in the Control of Adrenal Medullary Function

• Published in: Japanese Journal of Pharmacology 1995, Vol.67 (suppl.1), p.62-62
• Main Authors: Wakade, Arun R., Guo, Xi, Wakade, Taruna, Przywara, Dennis A.
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)46219-7

We have established the importance of neuropeptides 「vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP)」 as co-transmitters of splanchnic nerve endings in regulating synthesis and release of epinephrine (EPI) and norepinephrine (NE) in rat adrenal medulla. Acetylcholine (ACh) and peptides contribute differently at different levels of neuronal activity; VIP is released mostly at lower frequencies and ACh at higher frequencies. VIP and PACAP secrete mostly EPI, whereas ACh secretes EPI and NE. VIP and PACAP phosphorylate and produce catalytic activation of tyrosine hydroxylase. ACh has very little effect on these parameters. Using cultured rat chromaffin cells, microcarbon fiber electrodes and patch clamp techniques, we have determined the source of Ca^2+ necessary for the stimulation of exocytosis. ACh activated nicotinic (NIC) and muscarinic (MUS) receptors to induce secretion. NIC-evoked secretion was immediate and required extracellular Ca^2+ MUS-evoked secretion had a delay of ～3 sec, was long lasting and used intracelluiar Ca^2+ . PACAP-evoked secretion had the longest delay of ～6 sec, lasted as long as several min after 10 sec application, and required the presence of extracellular Ca^2+ . PACAP caused action potential firing without a significant change in inward current. We conclude that peptides and ACh recruit multiple receptors and signalling pathways to maintain secretion of catecholamines at rest and during stress.