A functional study of purinergic signalling in the normal and pathological rabbit corpus cavernosum.
OBJECTIVE
To examine rabbit cavernosal smooth muscle (CSM) relaxation to ATP, ADP and UTP in normal rabbits and in models of conditions that predispose to erectile dysfunction (ED), diabetes mellitus (DM; induced for 6 months) and bladder outlet obstruction (BOO, 6 weeks after surgery).


METHODS
Concentration-response curves (CRCs) were constructed to ATP, ADP and UTP on CSM from control rabbits in the absence and presence of antagonists. In addition, CRCs were constructed to ATP in CSM from rabbits with DM and BOO.


RESULTS
ATP and UTP caused equipotent, dose-dependent relaxations of pre-contracted normal rabbit CSM; ADP was more potent. Relaxation was inhibited by Reactive Blue 2, but not by suramin, 8-p-sulfophenyltheophylline or L-N(G)-nitroarginine methyl ester. In rabbits with DM and those with partial BOO, ATP-mediated CSM relaxation was less than in control rabbits. Pharmacological profiling suggests that purine-induced CSM relaxation might be mediated by P2Y(1) and P2Y(4) receptors in the rabbit.


CONCLUSIONS
In healthy rabbits, ATP released from nerves appears to produce relaxation of CSM via P2Y(4) receptors on smooth muscle, while ADP, acting on P2Y(1) receptors on endothelial cells, produces relaxation via nitric oxide. Alterations in CSM purinergic signalling might be implicated in the pathophysiology of ED associated with DM and BOO. Characterization of purinergic signalling in CSM might highlight new therapeutic targets for treating ED.
Calvert
Robert C
RC
Department of Urology, and Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, UK.
Khan
Masood A
MA
Thompson
Cecil S
CS
Mikhailidis
Dimitri P
DP
Burnstock
Geoffrey
G
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology; D018783:Impotence, Vasculogenic / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010413:Penis / Q000502:physiology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology
D011983:Receptors, Purinergic; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate