Protein kinase c regulates purinergic component of neurogenic contractions in mouse bladder.
OBJECTIVE
We evaluate the role of protein kinase C in excitatory purinergic neurotransmission in the mouse bladder.


METHODS
In isolated mouse detrusor strips contractile responses to electrical field stimulation were mostly mediated by neural released acetylcholine and adenosine triphosphate (ATP). The changes in neurotransmission were measured indirectly by recording the contraction of detrusor strips in response to repetitive electrical field stimulation by trains of electrical pulses at 8 Hz. 1 second in duration.


RESULTS
A protein kinase C activator, 1 to 2.5 nM. (beta-phorbol-12,13-dibutyrate (beta-PDBu), but not the inactive form alpha-phorbol-12,13-dibutyrate, significantly enhanced neurogenic detrusor contractions. The purinergic component of the evoked detrusor contractions in the presence of atropine was specifically sensitive to this enhancing effect by beta-PDBu but the cholinergic component in the alpha,beta-methylene ATP treated detrusors remained unaffected. This enhancing effect of beta-PDBu was dependent on the extracellular calcium (Ca2+) concentration. A P and/or Q type Ca2+ channel blocker, 0.1 and 0.3 microM. omega-conotoxin-MVIIC, and protein kinase C inhibitors, 0.3 and 1 microM. staurosporine and 0.3 and 1 microM. bisindolylmaleimide I but not 0.1 and 0.3 microM. omega-conotoxin-GVIA, an N type Ca2+ channel blocker, abolished the effect of beta-PDBu. Moreover, beta-PDBu did not affect the muscle responses induced by the exogenous agonists carbachol or alpha,beta-methylene ATP and potassium chloride.


CONCLUSIONS
These results suggest that the activation of Ca2+ channel, especially the P and/or Q type, may be involved in the enhancing effect of protein kinase C activator beta-PDBu on muscle contractions elicited by excitatory purinergic neurotransmission in the mouse detrusor strips.
Liu
S H
SH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin-Shiau
S Y
SY
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010703:Phorbol Esters; D011493:Protein Kinase C / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*
D015220:Calcium Channels; D010703:Phorbol Esters; D011983:Receptors, Purinergic; D011493:Protein Kinase C