ABSTRACT
In recent years, research on penile erection has increasingly been centered on the molecular mechanisms involved. Major progress has been made in the field and at present a whole number of neurotransmitters, chemical effectors, growth factors, second-messenger molecules, ions, intercellular proteins, and hormones have been characterized as components of the complex process of erection. This knowledge has led to the discovery of several new therapeutic targets and multiple medical approaches for the treatment of erectile dysfunction (ED). This review focuses on the progress made in this field within the last few years.
Subject(s)
Erectile Dysfunction/physiopathology , Erectile Dysfunction/therapy , Complementary Therapies , Cyclic AMP/physiology , Cyclic GMP/physiology , Humans , Hydrogen Sulfide/metabolism , Male , Nitric Oxide/physiology , Receptors, Adrenergic/physiology , Receptors, Angiotensin/physiology , Receptors, Endothelin/physiology , Regenerative Medicine , Signal Transduction , Stem Cell Transplantation , Tissue Engineering , Urotensins/physiology , Vasoconstriction/physiology , Vasodilation/physiology , rhoA GTP-Binding Protein/physiologySubject(s)
Histamine/pharmacology , Penis , Animals , Cimetidine/metabolism , Histamine/metabolism , Histamine H1 Antagonists/metabolism , Histamine H2 Antagonists/metabolism , Humans , Male , Mice , Penile Erection/drug effects , Penis/anatomy & histology , Penis/drug effects , Pyrilamine/metabolismABSTRACT
Soluble guanylyl cyclase (sGC) is the major effector molecule for nitric oxide (NO) and as such an interesting therapeutic target for the treatment of erectile dysfunction. To assess the functional importance of the sGCalpha(1)beta(1) isoform in corpus cavernosum (CC) relaxation, CC from male sGCalpha(1)(-/-) and wild-type mice were mounted in organ baths for isometric tension recording. The relaxation to endogenous NO (from acetylcholine, bradykinin and electrical field stimulation) was nearly abolished in the sGCalpha(1)(-/-) CC. In the sGCalpha(1)(-/-) mice, the relaxing influence of exogenous NO (from sodium nitroprusside and NO gas), BAY 41-2272 (NO-independent sGC stimulator) and T-1032 (phosphodiesterase type 5 inhibitor) were also significantly decreased. The remaining exogenous NO-induced relaxation seen in the sGCalpha(1)(-/-) mice was significantly decreased by the sGC-inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. The specificity of the impairment of the sGC-related responses was demonstrated by the unaltered relaxations seen with forskolin (adenylyl cyclase activator) and 8-pCPT-cGMP (cGMP analog). In conclusion, the sGCalpha(1)beta(1) isoform is involved in corporal smooth muscle relaxation in response to NO and NO-independent sGC stimulators. The fact that there is still some effect of exogenous NO in the sGCalpha(1)(-/- mice suggests the contribution of (an) additional pathway(s).
