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PACAP 38 is involved in the non‐adrenergic non‐cholinergic inhibitory neurotransmission in the pig urinary bladder neck
Author(s) -
Hernández Medardo,
Barahona María Victoria,
Recio Paz,
Bustamante Salvador,
Benedito Sara,
Rivera Luis,
GarcíaSacristán Albino,
Prieto Dolores,
Orensanz Luis M.
Publication year - 2006
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20287
Subject(s) - vasoactive intestinal peptide , endocrinology , medicine , neurotransmission , tetrodotoxin , methoctramine , guanethidine , muscarinic acetylcholine receptor , ppads , receptor antagonist , chemistry , receptor , neuropeptide , stimulation , antagonist , pirenzepine
Aims To investigate the role played by pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) in the non‐adrenergic non‐cholinergic (NANC) neurotransmission of the pig urinary bladder neck. Methods Urothelium‐denuded bladder neck strips were dissected and mounted in organ baths containing a physiological saline solution (PSS) at 37°C and gassed with 5% CO 2 and 95% O 2 , for isometric force recording. The relaxations to transmural nerve stimulation (EFS) or PACAP 38 were performed on strips precontracted with 1 µM phenylephrine (PhE). EFS experiments were carried out in the absence and the presence of guanethidine (10 µM), atropine (0.1 µM), and N G ‐nitro‐ l ‐arginine (L‐NOARG, 100 µM), to block noradrenergic neurotransmission, muscarinic receptors, and nitric oxide (NO) synthase, respectively. Results EFS (2–16 Hz, 1 ms duration, 20 sec trains, 75 mA current output) evoked frequency‐dependent relaxations which were reduced by the VIP/PACAP receptor antagonist PACAP (6–38) (3 µM), and by the neurotoxin of the capsaicin‐sensitive primary afferents capsaicin (10 µM), and abolished by the neuronal voltage‐activated Na + channel blocker tetrodotoxin (TTX, 1 µM). The vasoactive intestinal peptide (VIP) receptor antagonist [Lys 1 , Pro 2,5 , Arg 3,4 , Tyr 6 ]‐VIP (3 µM) failed to modify the EFS‐induced relaxations. PACAP 38 (1 nM–1 µM) induced concentration‐dependent relaxations which were reduced by PACAP (6–38), TTX and by the neuronal voltage‐gated Ca 2+ channel inhibitor ω‐conotoxin GVIA (ω‐CgTX, 1 µM). Conclusions The results suggest that PACAP 38, mainly released from capsaicin‐sensitive primary afferents, is involved in the NANC inhibitory neurotransmission of the pig urinary bladder neck, producing relaxation through neuronal and muscle VIP/PACAP receptor activation. Neurourol. Urodynam. © 2006 Wiley‐Liss, Inc.