Nitrergic Neurotransmission in the Lower Urinary Tract and Penile Erectile Tissues

Andersson, Karl‐Erik

doi:10.1007/978-1-4612-1328-4_4

Cited by 2 publications

(2 citation statements)

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“…The control of smooth muscle tone of the male reproductive tract is a complex biological interaction involving multiple biochemical signals deriving from neuronal, endothelial, and glandular sources [1,2]. To date, it is well‐established that the cyclic nucleoside monophosphates cyclic AMP (cAMP) and cyclic GMP (cGMP) are involved in the maintenance of the normal function of human genital tissues.…”

Section: Introductionmentioning

confidence: 99%

Effects of Phosphodiesterase Inhibitors on the Contractile Responses of Isolated Human Seminal Vesicle Tissue to Adrenergic Stimulation

Ückert

Bazrafshan

Sonnenberg³

et al. 2009

The Journal of Sexual Medicine

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Introduction It has been suggested that the capability of the phosphodiesterase 5 (PDE5) inhibitor sildenafil citrate (VIAGRA) to retard the ejaculatory response may include modulation of the contraction of seminal vesicle (SV) smooth muscle. In fact, it has been shown that PDE inhibitors can reverse the tension of isolated human SV tissue and enhance the production of cyclic AMP and cyclic GMP. Aim The aim of this study was to examine the effects of selective phosphodiesterase (PDE) inhibitors on both the spontaneous and electrically induced phasic contractions of isolated human SV smooth muscle. Main Outcome Measures To measure the inhibition exerted by PDE inhibitors vinpocetine (PDE1-inhibitor), rolipram (PDE4-inhibitor), sildenafil, and vardenafil (PDE5-inhibitors) on the phasic contractile response of isolated SV tissue. Methods Using the organ bath technique, the effects of increasing concentrations of the PDE inhibitors (1 nM–10 µM) were investigated on phasic contractions of SV tissue strips either mediated by means of electrical field stimulation (EFS) or the alpha1-adrenoceptor agonist norepinephrine. Results The contractile activity in response to EFS was dose-dependently reversed by the PDE inhibitors. The rank order of efficacy was: rolipram > sildenafil ≥ vardenafil > vinpocetine. Mean maximum inhibition of contraction was determined as −89.6% (rolipram), −61.3% (sildenafil), −62% (vardenafil), and −46% (vinpocetine). No differences were registered with regard to the effects of sildenafil and vardenafil on the inhibition of the contraction amplitudes. The frequency of the spontaneous contractions (amplitudes/5 minutes) was reduced by 50% in the presence of 2 µM rolipram, 5 µM sildenafil or vardenafil, and 8 µM vinpocetine. Conclusion Our results demonstrate that PDE inhibitors can inhibit EFS-induced and spontaneous contractile activity of isolated human SV tissue. These findings might be of importance with regard to the pharmacological treatment of premature ejaculation.

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Section: Introductionmentioning

confidence: 99%

Effects of Phosphodiesterase Inhibitors on the Contractile Responses of Isolated Human Seminal Vesicle Tissue to Adrenergic Stimulation

Ückert

Bazrafshan

Sonnenberg³

et al. 2009

The Journal of Sexual Medicine

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“…In the bladder body a predominant b-adrenoceptor population mediates relaxation to noradrenaline. Thus, drugs with b-adrenoceptor agonist activity inhibit nerve-induced contractions of detrusor muscle in vitro, and the administration of these drugs in humans can increase bladder capacity [3]. The distribution of b-adrenoceptor subtypes is species dependent, the predominant subtype being the b 1 -adrenoceptor in some species such as the cat [40], and the b 2 -adrenoceptor in others such as the rabbit [44].…”

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confidence: 97%

Potential therapeutic targets for treatment of the overactive bladder

2001

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Muscarinic receptor antagonists remain the main therapy for the treatment of the overactive bladder yet severe adverse effects make them unsuitable for a large number of patients. The development of new drugs with novel mechanisms of action for the treatment of this condition is therefore essential. This article considers some of the targets currently under investigation for the development of such compounds. Beta-adrenoceptor agonists and KATP channel openers inhibit detrusor muscle activity and remain targets for drug development. There is also evidence that alpha-adrenoceptor antagonists may be effective in the overactive bladder, but the mechanism involved in this action is unclear. Finally the role of tachykinins in regulating bladder function through both the sensory and the motor innervation make them a potential target for drug development, but as with the the others, a selective action on the bladder must remain the goal of drug development.

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Nitrergic Neurotransmission in the Lower Urinary Tract and Penile Erectile Tissues

Cited by 2 publications

References 182 publications

Effects of Phosphodiesterase Inhibitors on the Contractile Responses of Isolated Human Seminal Vesicle Tissue to Adrenergic Stimulation

Effects of Phosphodiesterase Inhibitors on the Contractile Responses of Isolated Human Seminal Vesicle Tissue to Adrenergic Stimulation

Potential therapeutic targets for treatment of the overactive bladder

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