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Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
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Purinergic modulation of human corpus cavernosum relaxation
D H W Lau1, M J Metcalfe, F H Mumtaz
1Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, University College London, London, UK.
International Journal of Andrology
|November 1, 2007
Summary
Activation of P2Y(6) receptors in human cavernosal tissue causes smooth muscle relaxation. This relaxation is independent of neuronal and nitric oxide pathways, suggesting a novel mechanism for penile erection regulation.
Area of Science:
- Urology
- Pharmacology
- Physiology
Background:
- P2Y(6) receptors are known to influence vascular smooth muscle.
- Their role in human cavernosal function remains unclear.
Purpose of the Study:
- To investigate the effect of P2Y(6) receptor activation on human cavernosal smooth muscle.
- To determine the mechanism of P2Y(6) receptor-mediated cavernosal responses.
Main Methods:
- Human cavernosal tissue was obtained and analyzed for P2Y(6) receptor expression using immunohistochemistry and Western blotting.
- Organ bath studies assessed the effects of UDP (P2Y(6) agonist) and cibacron blue 3GA (P2Y(6) antagonist) on phenylephrine-pre-contracted cavernosal strips.
- Electrical field stimulation was used to evaluate neuronal contributions.
Main Results:
- P2Y(6) receptors were confirmed in human corpus cavernosum.
- UDP induced significant dose-dependent relaxation of cavernosal smooth muscle.
- This relaxation was blocked by cibacron blue 3GA but not by L-NAME, indicating a non-neuronal, non-nitric oxide dependent pathway.
- Electrical field stimulation-induced relaxations were not affected by P2Y(6) antagonism.
Conclusions:
- P2Y(6) receptor activation induces relaxation in human cavernosal smooth muscle.
- The mechanism is independent of neuronal signaling and nitric oxide.
- P2Y(6) receptors represent a potential target for modulating erectile function.
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