Ectonucleotidases and Purinergic Receptors in Mouse Prostate Gland

Abstract

Extracellular ATP/ADP and its metabolite adenosine are important signaling molecules that regulate cellular function by binding to P2 and P1/adenosine receptors. The kinetics of these signaling molecules are critically modulated by ectonucleotidases, enzymes that convert ATP/ADP to adenosine. Although the expression and function of these enzymes and relevant purinergic receptors in the prostate gland are not well understood, recent reports indicate impaired ATP hydrolysis activity in the aging prostate. Purinergic signaling is known for its role in inflammation, muscle contraction, pain sensation, and cell proliferation in many systems, suggesting its potential importance in normal prostate function and pathological conditions such as benign prostatic hyperplasia and prostatitis. To better understand purine-converting enzymes and purinergic receptors in the prostate, we isolated mouse prostate glands for immunofluorescent staining and microscopy imaging using specific antibodies. Our study identified a differential expression profile of purinergic enzymes and receptors in the prostate: ENTPD1 and P2x1 receptors predominantly in prostate smooth muscle cells, ENTPD2 and NT5E in prostate interstitial cells, and ALPL in prostate epithelial cells. Functionally, in addition to the P2x1-mediated prostate smooth muscle contraction induced by agonist ,{beta}-meATP, we observed an ATP{gamma}S-induced contraction force after P2x1 desensitization. This led to the identification of multiple P2Y receptors in mouse prostate smooth muscle, including P2Y1, P2Y2, and P2Y11 receptors, which potentially mediate the ATP{gamma}S-induced contraction force. These discoveries lay the foundation for further mechanistic understanding of how purinergic signaling regulates prostate function and dysfunction in both rodents and potentially humans.