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Title: PACAP 38 is involved in the non-adrenergic non-cholinergic inhibitory neurotransmission in the pig urinary bladder neck. Author: Hernández M, Barahona MV, Recio P, Bustamante S, Benedito S, Rivera L, García-Sacristán A, Prieto D, Orensanz LM. Journal: Neurourol Urodyn; 2006; 25(5):490-7. PubMed ID: 16721838. Abstract: 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 degrees 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 microM phenylephrine (PhE). EFS experiments were carried out in the absence and the presence of guanethidine (10 microM), atropine (0.1 microM), and N(G)-nitro-L-arginine (L-NOARG, 100 microM), 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 microM), and by the neurotoxin of the capsaicin-sensitive primary afferents capsaicin (10 microM), and abolished by the neuronal voltage-activated Na(+) channel blocker tetrodotoxin (TTX, 1 microM). The vasoactive intestinal peptide (VIP) receptor antagonist [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (3 microM) failed to modify the EFS-induced relaxations. PACAP 38 (1 nM-1 microM) induced concentration-dependent relaxations which were reduced by PACAP (6-38), TTX and by the neuronal voltage-gated Ca(2+) channel inhibitor omega-conotoxin GVIA (omega-CgTX, 1 microM). 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.[Abstract] [Full Text] [Related] [New Search]