Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery

Abstract

Activation of adenosine receptors (ARs) has been implicated in the modulation of renal and cardiovascular systems, as well as erectile functions. Recent studies suggest that adenosinemediated regulation of erectile function is mainly mediated through A 2B AR activation. However, no studies have been conducted to determine the contribution of AR subtype in the regulation of the vascular tone of the pudendal artery (PA), the major artery supplying and controlling blood flow to the penis. Our aim was to characterize the contribution of AR subtypes and identify signaling mechanisms involved in adenosine-mediated vascular tone regulation in the PA. We used a DMT wire myograph for muscle tension measurements in isolated PAs from wild-type, A 2A AR knockout, A 2B AR knockout, and A 2A /A 2B AR double-knockout mice. Real-time reverse transcription-polymerase chain reaction was used to determine the expression of the AR subtypes. Data from our pharmacologic and genetic approaches suggest that AR activation-mediated vasodilation in the PA is mediated by both the A 2A AR and A 2B AR, whereas neither the A 1 AR nor A 3 AR play a role in vascular tone regulation of the PA. In addition, we showed that A 2A AR-and A 2B AR-mediated vasorelaxation requires activation of nitric oxide and potassium channels; however, only the A 2A ARmediated response requires protein kinase A activation. Our data are complemented by mRNA expression showing the expression of all AR subtypes with the exception of the A 3 AR. AR signaling in the PA may play an important role in mediating erection and represent a promising therapeutic option for the treatment of erectile dysfunction.

Dysregulation of adenosine kinase isoforms in breast cancer

“…ADK-L is reported to affect epigenetic remodeling [19,20] and is thought to preferentially function as a regulator of methyltransferase action through clearance of adenosine [17,21]. On the other hand, ADK-S regulates extracellular adenosine concentration to activate various adenosine receptor subtypes and affects angiogenesis [22], inflammation [20], and immune suppression [23]. These functions of ADK isoforms strongly support a differential role for ADK-L versus ADK-S in cancer.…”

Effect of low androgen status on the expression of adenosine A 2A and A 2B receptors in rat penile corpus cavernosum

“…It demonstrates that A 2B is the primary receptor for CCSs relaxation in response to adenosine (Mi et al, ). A study has reported that A 2A and A 2B adenosine receptors mediate vasodilation of the pudendal artery, while A 1 and A 3 receptors are not involved in regulation of vasodilation (Labazi, Tilley, Ledent, & Mustafa, ). The mouse cavernosal strips’ tension was measured after the use of A 2A and A 2B receptor agonists and inhibitors, and it was found that adenosine can relax smooth muscle and induce penile erection by activating the A 2A and A 2B receptors (Tostes et al, ).…”

Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries

“…On the other hand, P2Y1 receptor stimulation with either 2-MeSADP or ADP vasodilates rat mesenteric arteries 80–100% yet only relaxes IPA by 5–15% [25] . ADP elicited a 10% greater relaxation in the proximal IPA which could be attributed to increased ectonuclease mediated ADP hydrolysis into adenosine and subsequent activation of NO-independent adenosine receptors to regulate cAMP [26] . The role of adenosine receptors in facilitating an erection in not yet completely understood.…”

“…The role of adenosine receptors in facilitating an erection in not yet completely understood. Adenosine receptors (A2A and A2B) have been identified to play a functional role in mouse IPA NO dependent vasodilation [26] . Our findings show distal IPA, but not proximal IPA, relax through NANC mediated NO-dependent modulation of cGMP.…”