Beyond The Abstract A Functional Study Of Purinergic Signalling In The Normal And Pathological Rabbit Corpus Cavernosum

Main Category: Urology / Nephrology
Article Date: 23 Mar 2008 - 0:00 PDT

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UroToday.com - Adenosine-triphopshate (ATP) acts as an extracellular signalling molecule via specific receptors (P2-purinoceptors) and urological research has largely focused on its actions in the bladder, where, along with acetyl choline, it contributes to the initiation of detrusor contraction in normal lower mammals and the pathological human bladder. ATP also modifies smooth muscle tone in many vascular systems and can cause either smooth muscle relaxation or contraction depending on the receptor subtype expression. The modified blood vessel that is the corpus cavernosum is no exception and ATP is known to cause cavernosal smooth muscle relaxation and in vivo injection of ATP into the corpus cavernosum of dogs causes penile erection. Although nitric oxide is the principle neurotransmitter in the corpus cavernosum, other neurotransmitter systems that may be redundant under normal physiological circumstances (e.g. prostaglandins) may nevertheless provide important pharmacological targets. Indeed, the most effective pharmacological treatment currently available for erectile dysfunction acts via such systems. Understanding of the mechanisms of action of ATP is important so that new therapies might be more specifically targeted with the development of purinoceptor-subtype specific agonists. Earlier studies have provided some conflicting evidence as to the mechanism of action of ATP.

This study uses pharmacological profiling to characterise the purinoceptor-subtypes mediating cavernosal smooth muscle relaxation in the rabbit. The results suggest that ATP released from nerves relaxes caversonal smooth muscle via P2Y4-receptors, but also that ATP after enzymatic conversion to adenosine diphosphate (ADP) may also cause smooth muscle relaxation via P2Y1-receptors on endothelial cells which release nitric oxide. This may also clarify some of the apparent contradictions of earlier studies. In addition, this study identifies some abnormalities in cavernosal smooth muscle purinergic signalling in models of erectile dysfunction associated with diabetes mellitus and bladder outlet obstruction. Pharmacological profiling can give useful information about which receptors have functional activity but this information needs to be supported by other techniques such as Northern blotting, in-situ hybridisation or immunohistochemistry which this study did not address.

Many erectile dysfunction patients fail PDE5-inhibitor treatment and purinoceptor agonists, whether alone, or as a combination therapy may have therapeutic potential.

Written by Geoffrey Burnstock, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

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