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      Physiological and pharmacological aspects of the vas deferens—an update


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          The vas deferens, a muscular conduit conveying spermatozoa from the epididymis to the urethra, has been used as a model tissue for smooth muscle pharmacological and physiological advancements. Many drugs, notably α-adrenergic antagonists, have effects on contractility and thus normal ejaculation, incurring significant side effects for patients that may interfere with compliance. A more thorough understanding of the innervation and neurotransmitter pharmacology of the vas has indicated that this is a highly complex structure and a model for co-transmission at the synapse. Recent models have shown clinical scenarios that alter the vas contraction. This review covers structure, receptors, neurotransmitters, smooth muscle physiology, and clinical implications of the vas deferens.

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          Most cited references141

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          Signal transduction and regulation in smooth muscle.

          A P Somlyo (1994)
          Smooth muscle cells in the walls of many organs are vital for most bodily functions, and their abnormalities contribute to a range of diseases. Although based on a sliding-filament mechanism similar to that of striated muscles, contraction of smooth muscle is regulated by pharmacomechanical as well as by electromechanical coupling mechanisms. Recent studies have revealed previously unrecognized contractile regulatory processes, such as G-protein-coupled inhibition of myosin light-chain phosphatase, regulation of myosin light-chain kinase by other kinases, and the functional effects of smooth muscle myosin isoforms. Abnormalities of these regulatory mechanisms and isoform variations may contribute to diseases of smooth muscle, and the G-protein-coupled inhibition of protein phosphatase is also likely to be important in regulating non-muscle cell functions mediated by cytoplasmic myosin II.
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            Calcium sparks in smooth muscle.

            Local intracellular Ca(2+) transients, termed Ca(2+) sparks, are caused by the coordinated opening of a cluster of ryanodine-sensitive Ca(2+) release channels in the sarcoplasmic reticulum of smooth muscle cells. Ca(2+) sparks are activated by Ca(2+) entry through dihydropyridine-sensitive voltage-dependent Ca(2+) channels, although the precise mechanisms of communication of Ca(2+) entry to Ca(2+) spark activation are not clear in smooth muscle. Ca(2+) sparks act as a positive-feedback element to increase smooth muscle contractility, directly by contributing to the global cytoplasmic Ca(2+) concentration ([Ca(2+)]) and indirectly by increasing Ca(2+) entry through membrane potential depolarization, caused by activation of Ca(2+) spark-activated Cl(-) channels. Ca(2+) sparks also have a profound negative-feedback effect on contractility by decreasing Ca(2+) entry through membrane potential hyperpolarization, caused by activation of large-conductance, Ca(2+)-sensitive K(+) channels. In this review, the roles of Ca(2+) sparks in positive- and negative-feedback regulation of smooth muscle function are explored. We also propose that frequency and amplitude modulation of Ca(2+) sparks by contractile and relaxant agents is an important mechanism to regulate smooth muscle function.
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              Smooth muscle cell calcium activation mechanisms.

              Smooth muscle cell (SMC) contraction is controlled by the Ca2+ and Rho kinase signalling pathways. While the SMC Rho kinase system seems to be reasonably constant, there is enormous variation with regard to the mechanisms responsible for generating Ca2+ signals. One way of dealing with this diversity is to consider how this system has been adapted to control different SMC functions. Phasic SMCs (vas deferens, uterus and bladder) rely on membrane depolarization to drive Ca2+ influx across the plasma membrane. This depolarization can be induced by neurotransmitters or through the operation of a membrane oscillator. Many tonic SMCs (vascular, airway and corpus cavernosum) are driven by a cytosolic Ca2+ oscillator that generates periodic pulses of Ca2+. A similar oscillator is present in pacemaker cells such as the interstitial cells of Cajal (ICCs) and atypical SMCs that control other tonic SMCs (gastrointestinal, urethra, ureter). The changes in membrane potential induced by these cytosolic oscillators does not drive contraction directly but it functions to couple together individual oscillators to provide the synchronization that is a characteristic feature of many tonic SMCs.

                Author and article information

                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                18 June 2013
                22 August 2013
                : 4
                : 101
                [1] 1Wake Forest Baptist Medical Center, Medical Center Boulevard Winston-Salem, NC, USA
                [2] 2Institute for Regenerative Medicine, Wake Forest University School of Medicine Winston-Salem, NC, USA
                Author notes

                Edited by: Ulf Simonsen, Aarhus University, Denmark

                Reviewed by: Yoh Takuwa, Kanazawa University Graduate School of Medical Sciences, Japan; Ruth A. Elliott, University of Leicester, UK

                *Correspondence: Karl-Erik Andersson, Institute for Regenerative Medicine, Wake Forest University School of Medicine, 391 Technology Way, Winston-Salem, NC 27101, USA e-mail: karl-erik.andersson@ 123456med.lu.se

                This article was submitted to Integrative and Regenerative Pharmacology, a section of the journal Frontiers in Pharmacology.

                Copyright © 2013 Koslov and Andersson.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 21 May 2013
                : 29 July 2013
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 150, Pages: 11, Words: 10691
                Review Article

                Pharmacology & Pharmaceutical medicine
                vas deferens,smooth muscle,adrenergic receptors,contraction,fertility,purinergic receptors


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