Effect of vasoactive intestinal peptide (VIP)‐related peptides on cholinergic neurogenic and direct mucus secretion in ferret trachea in vitro

• Published in: British journal of pharmacology Vol. 128; no. 6; pp. 1353 - 1359
• Main Authors: Liu, Yu‐Chih, Khawaja, Aamir M, Rogers, Duncan F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1999; Nature Publishing
• Subjects: Acetylcholine - pharmacology; Airways; Animals; Atropine - pharmacology; Binding, Competitive - drug effects; Biological and medical sciences; Cholinergic Fibers - physiology; cholinergic nerve; Dose-Response Relationship, Drug; Drug Synergism; Electric Stimulation; Ferrets; In Vitro Techniques; Male; Medical sciences; mucus; Mucus - drug effects; Mucus - secretion; nerves; Neuropeptides - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Phentolamine - pharmacology; Piperidines - pharmacology; pituitary adenylate cyclase activating peptide; Pituitary Adenylate Cyclase-Activating Polypeptide; Propranolol - pharmacology; Receptors, Vasoactive Intestinal Peptide - metabolism; secretin; Secretin - pharmacology; Trachea - drug effects; Trachea - innervation; Trachea - secretion; vasoactive intestinal peptide; Vasoactive Intestinal Peptide - pharmacology; Fissipedia; Cholinergic neuron; Carnivora; Secretion; Secretin; Mucus; Biological activity; Vertebrata; Mammalia; Animal; Ferret; Vasoactive intestinal peptide; Trachea; Pituitary adenylate cyclase activating peptide; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702942

We investigated whether vasoactive intestinal peptide (VIP) and its related peptides, pituitary adenylate cyclase activating peptide (PACAP) and secretin, regulate cholinergic neural mucus secretion in ferret trachea in vitro, using 35SO4 as a mucus marker. We also studied the interaction between VIP and secretin on cholinergic mucus output. VIP (1 and 10 μM) increased secretion, whereas neither PACAP1–27, PACAP1–38 nor secretin (up to 10 μM) increased mucus output. In contrast, VIP, PACAP1–27 and PACAP1–38 concentration‐dependently inhibited cholinergic neural secretion, with an order of potency of VIP>PACAP 1–38>PACAP1–27. Neither PACAP1–27 nor PACAP1–38 altered the secretion induced by acetylcholine (ACh). Secretin increased cholinergic neural secretion with a maximal increase of 190% at 1 μM. This potentiation was blocked by VIP or atropine. Similarly, secretin (1 μM) potentiated VIP (1 μM)‐induced mucus output by 160%. Secretin did not alter exogenous ACh‐induced secretion. VIP vs secretin competition curves suggested these two peptides were competing reversibly for the same receptor. We conclude that, in ferret trachea in vitro, VIP and PACAPs inhibit cholinergic neural secretion via pre‐junctional modulation of cholinergic neurotransmission. VIP and secretin compete for the same receptor, possibly a VIP1 receptor, at which secretin may be a receptor antagonist. British Journal of Pharmacology (1999) 128, 1353–1359; doi:10.1038/sj.bjp.0702942