Management of erectile function by penile purinergic p2 receptors in the diabetic rat.
OBJECTIVE
We determined the role of purine and pyrimidine nucleotides in erectile function in diabetic rats.


METHODS
A total of 60 adult male rats were divided into 2 groups, including 30 controls and 30 treated with streptozotocin (60 mg/kg) for 8 weeks to induce hyperglycemia. Changes in intracavernous pressure after intracrural injections of adenosine 5'triphosphate and adenosine 5'triphosphate analogues in control and diabetic rats, and the relaxant response to electrical field stimulation of precontracted corpus cavernosum smooth muscle in organ baths were investigated. The localization of P2X1, P2Y1 and P2Y2 receptors was assessed in penile tissue via an immunohistochemical approach.


RESULTS
Corpus cavernosum smooth muscle relaxation in vivo and by electrical field stimulation in vitro was significantly decreased in diabetic rats. Adenosine 5'triphosphate (P2X, P2Y), 2-methylthioadenosine 5'triphosphate (P2Y1) and uridine 5'-triphosphate (P2Y2) agonists but not alpha,beta-methylene adenosine 5'triphosphate (a P2X1 agonist) significantly improved the erectile response to electrical field stimulation in diabetic rat corpus cavernosum smooth muscle. Although intracavernous pressure/mean arterial pressure values in the rats were not restored in the presence of the P2X1 antagonist PPADS, the relaxation response to electrical field stimulation in isolated corpus cavernosum smooth muscle from diabetic rats was improved. Abundant immunoreactivity for PX1 and P2Y2 receptors was observed in penile tissues from diabetic rats compared to that from control rats.


CONCLUSIONS
These results demonstrate 1) heterogeneous effects of purinergic agonists on corporeal function in diabetic rats, and 2) the activation of P2Y1 and P2Y2 receptor relaxation of corpus cavernosum smooth muscle to induce erection in rats and perhaps improve erectile function in men with diabetes.
Gur
Serap
S
Department of Urology and Pharmacology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
Kadowitz
Philip J
PJ
Abdel-Mageed
Asim B
AB
Kendirci
Muammer
M
Sikka
Suresh C
SC
Burnstock
Geoffrey
G
Hellstrom
Wayne J G
WJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D012016:Reference Values; D012680:Sensitivity and Specificity; D013311:Streptozocin / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D013872:Thionucleosides; C021714:2-methylthioadenosine; D013311:Streptozocin; D000255:Adenosine Triphosphate; D000241:Adenosine; D014544:Uridine Triphosphate