PACAP 38 is involved in the non-adrenergic non-cholinergic inhibitory neurotransmission in the pig urinary bladder neck.
OBJECTIVE
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.
Hernández
Medardo
M
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. medardo@farm.ucm.es
Barahona
María Victoria
MV
Recio
Paz
P
Bustamante
Salvador
S
Benedito
Sara
S
Rivera
Luis
L
García-Sacristán
Albino
A
Prieto
Dolores
D
Orensanz
Luis M
LM
D000109:Acetylcholine / Q000502:physiology; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000502:physiology; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology / Q000502:physiology*; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D009498:Neurotoxins; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); C100831:vasoactive intestinal peptide, Lys(1)-Pro(2,5)-Arg(3,4)-Tyr(6)-; D019335:Nitroarginine; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001285:Atropine; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D002211:Capsaicin; D004837:Epinephrine; D006145:Guanethidine