Female pig urethral tone is dependent on Rho guanosine triphosphatases and Rho-associated kinase.
OBJECTIVE
Circular smooth muscle of the urethra generates spontaneous myogenic tone of relevance for the maintenance of continence. We tested if Rho guanosine triphosphatases (GTPases) and Rho-associated kinase (ROK) are involved in the generation of urethral tone.


METHODS
Small circular strips of female pig urethra were dissected out and mounted for recording isometric force. The effect of pharmacological agents known to modulate the activity of Rho GTPases or ROK was examined. The intracellular calcium concentration was measured using fura-2.


RESULTS
Urethral tone was abolished by removing extracellular calcium or by adding the calcium antagonist felodipine. The decrease in force was closely related to a decrease in intracellular calcium concentration, indicating that tone depends on membrane associated mechanisms. Toxin B, which inactivates Rho GTPases, and Y 27632, which inhibits ROK, completely abolished tone in the female pig urethra. The latter effect occurred without any change in the intracellular calcium concentration.


CONCLUSIONS
The results suggests that urethral tone depends on activity in G-protein coupled pathways and inhibition of this activity is sufficient for urethral tone relaxation. Thus, to our knowledge a new pathway in the generation of urethral tone, which might be acted on by autonomic nerves during micturition, has been identified.
Malmqvist
Ulf
U
Department of Clinical Pharmacology, University of Lund, Sweden.
Hedlund
Petter
P
Swärd
Karl
K
Andersson
Karl-Erik
KE
D000577:Amides / Q000494:pharmacology; D000818:Animals; D005260:Female; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012235:Rhodamines; D013552:Swine; D014521:Urethra / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D009125:Muscle Relaxants, Central; D011725:Pyridines; D012235:Rhodamines; C094415:guanosine triphosphate-rhodamine; C108830:Y 27632; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases