[Bladder and cavernous contractility and relaxation among intracellular messengers, changes in sarcoplasmatic free...

During the last decade, the cellular pathways involved in excitation-contraction coupling have been identified and explained. The key event in the initiation of the contraction is the rise in sarcoplasmic free calcium. Inositol 1,4,5-triphosphate (IP3) and cyclic nucleotides (cAMP, cGMP) have been demonstrated to be the second messengers associated with stimulation of smooth muscle selective receptor-subtypes (cholinergic, adrenergic, non adrenergic-non cholinergic) by specific neuromodulators. Furthermore, activation of voltage-gated L type- or receptor operated calcium channels is involved in the sarcoplasmic free calcium changes. KCa and KATP-channels play an important role in smooth muscle hyperpolarization; KATP-openers excite great interest as therapeutic agents for the detrusor instability. The specificity of different receptor subtypes and their transductional pathways has increased the number of targets for drug treatment of urinary bladder disorders and erectile dysfunction. As the level of intracellular nucleotide second messengers can be modulated by tissue-specific phosphodiesterase (PDE) isoenzymes, PDEs selective inhibitors have the potential to exert organ-specific therapeutic effects. So, PDE I selective inhibitor vinpocetine has been proposed for the symptomatic treatment of detrusor instability; PDE V selective inhibitor sildenafil, enhancing the NO-cGMP pathway-mediated cavernosal smooth muscle relaxation, is an effective drug to treat erectile dysfunction.