Coupling of α₁-Adrenoceptors to ERK1/2 in the Human Prostate

Abstract

Introduction: α₁-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α₁-adrenoceptor functions besides contraction. Here, we investigated whether α₁-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 µM) or phenylephrine (10 µM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 µM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: α₁-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α₁-adrenoceptors in the regulation of prostate growth.

MAP Kinase-Mediated and MLCK-Independent Phosphorylation of MLC20 in Smooth Muscle Cells

“…Similar role of ERK1/2 are also observed in other smooth muscle (cells) (Jeong et al, 2011). However, some reports show that the inhibitors of ERK and its upstream do not affect vascular smooth muscle contraction (Do et al, 2009;Bauer et al, 2011;Sathish et al, 2011). Thus, this role of ERK in regulation of smooth muscle contraction is not universal, or even controversial.…”

Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate

“…Apart from these contractile signaling mechanisms, some evidence for coupling to non-motoric pathways has been provided. This includes the extracellular signal-regulated kinases (ERK1/2) and p38 mitogen-activated protein kinase (Kanagawa et al, 2003;Bauer et al, 2011;Strittmatter et al, 2011). According to our current findings, this model has to be extended by the Akt pathway.…”

“…Similar to Akt, prostate α1-adrenoceptors are coupled to ERK1/2 (Kanagawa et al, 2003;Bauer et al, 2011). Akt and ERK1/2 are common regulators of cell cycle, growth, and differentiation, including smooth muscle cells (Chang and Karin, 2001;Franke, 2008;Morello et al, 2009;Liao and Hung, 2010).…”

“…However, a regression of prostate volume did not become apparent during the widespread application of α1-adrenoceptor blockers. It has been assumed that the α1-adrenergic regulation is just one of different mediators of prostate growth and hyperplasia (Bauer et al, 2011). In vivo, androgens, growth factors and hormones may contribute to prostate growth simultaneously with α1-adrenoceptors (Royuela et al, 1998;Lucia and Lambert, 2008).…”

“…However, any non-motoric signaling by α1-adrenoceptors in the human prostate is still poorly understood. Based on observations in patients with prostate hyperplasia, it has been proposed that α1-adrenoceptors may be one of various regulators of prostate growth, which act in concert with other mediators (Kyprianou and Jacobs, 2000;Bauer et al, 2011). Together, these previous findings demonstrated that intracellular signaling by prostate α1-adrenoceptors still needs improved understanding, despite the enormous relevance of these receptors for prostate physiology and in therapy of LUTS.…”