Signal transduction in cavernous smooth muscle

Abstract

Knowledge of intracellular signal propagation in smooth-muscle tone regulation is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction and the development of new and selective pharmacological agents in the treatment of erectile dysfunction. Cavernous smooth-muscle tone depends heavily on the amount of intracellular free Ca2+. In the resting state the sarcoplasmic free Ca2+ amounts to about 120-270 nM, whereas in the extracellular fluid the Ca2+ level is in the range of 1.5-2 mM. Electromechanical and pharmacomechanical coupling induces an increase in the levels of free sarcoplasmic Ca2+ by a factor of 2-3 to 550-700 nM that triggers myosin phosphorylation and subsequent smooth muscle contraction. In this case, modulation of membrane-bound ion channels and regulation of the intracellular second-messenger system are attractive and feasible targets for pharmacological intervention. Besides the amount of free sarcoplasmic Ca2+, smooth-muscle tone is also modulated by the regulation of Ca2+ sensitivity ("Ca-sensitization") and Ca(2+)-independent contraction processes.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…In general, smooth muscle contraction is controlled by Ca 2ϩ and Rho kinase signaling pathways (Berridge, 2008). Changes in the sarcoplasmic Ca 2ϩ concentration, and thereby in the contractile state of the smooth muscle cell, can occur with or without changes in the membrane potential Somlyo, 1994, 2000;Stief et al, 1997;Berridge, 2008) (Fig. 6).…”

Vasoconstriction, RhoA/Rho-kinase and the erectile response

“…7,17 The principle agent leading to penile smooth muscle relaxation is NO released by the autonomic innervation of the erectile tissue and by arteriolar and cavernosal endothelial cells. 18 NO diffuses into smooth muscle cells where it activates soluble guanylate cyclase elevating intracellular levels of cyclic GMP and activating cyclic GMP-dependent protein kinase (PKG).…”

Intracavernous administration of SIN-1+VIP in an in vivo rabbit model for erectile function

“…In the smooth muscle, cGMP and cAMP do not only show their effect through Ca 2þ , several other mechanisms have also been suggested. 6 As mentioned in the introduction, the principal neurotransmitter mediating these alterations for trabecular smooth muscle relaxation in the corpora cavernosa is characterized as a NANC neurotransmitter. This is supported by in vivo and in vitro experiments.…”