Mechanisms involved in the nitric oxide independent inhibitory neurotransmission to the pig urinary bladder neck.
OBJECTIVE
The current study investigates the mechanisms involved in nitric oxide (NO)-independent, nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission to the pig urinary bladder neck.


METHODS
Urothelium-denuded strips were mounted in organ baths containing physiological saline solution (PSS) at 37°C for isometric force recordings. The relaxations to electrical field stimulation (EFS) were carried out on strips treated with guanethidine, atropine and N(G) -nitro-L-arginine, to block noradrenergic neurotransmission, muscarinic receptors and NO synthase, respectively, and precontracted with phenylephrine.


RESULTS
EFS (1-16 Hz) produced frequency-dependent relaxations which were abolished by the blockade of neuronal voltage-activated Na(+) channels. Nonselective and selective inhibition of COX and COX-1, respectively, and blockade of Na(+) -K(+) ATPase reduced the EFS-induced relaxations. However, blockade of COX-2, soluble guanylyl cyclase, large-, intermediate- and small-conductance Ca(2+) -activated K(+) channels, ATP-dependent K(+) channels, voltage-gated K(+) channels, cAMPc-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) failed to modify the nerve-mediated relaxations.


CONCLUSIONS
The NO-independent inhibitory neurotransmission to the pig urinary bladder neck is mediated, in part, through prostanoids release from a COX-1 pathway, and through activation of the Na(+) -K(+) ATPase. PKA and PKG pathways and postjunctional K(+) channels do not appear to be involved in the NO-independent nerve-mediated relaxations.
Martínez-Saénz
Ana
A
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Barahona
María Victoria
MV
Orensanz
Luis M
LM
Recio
Paz
P
Bustamante
Salvador
S
Benedito
Sara
S
Carballido
Joaquín
J
García-Sacristán
Albino
A
Prieto
Dolores
D
Hernández
Medardo
M
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D001285:Atropine; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine