Effects Of Alpha 1-adrenoceptor Antagonists Research Articles

Differential Effects of Alpha 1-Adrenoceptor Antagonists on the Postsynaptic Sensitivity: Using Slice Patch-Clamp Technique for Inhibitory Postsynaptic Current in Substantia Gelatinosa Neurons From Lumbosacral Spinal Cord in Rats.

PurposeAlpha1-adrenoceptors participate in improving storage symptoms of male lower urinary tract symptoms. However, the mechanism of action of these compounds remains unclear. The goal of the present study was to clarify the effect of α1- adrenoceptor antagonists on γ-aminobutyric acid (GABA)/glycine-mediated outward currents of the inhibitory postsynaptic current (IPSC) in substantia gelatinosa (SG) neurons from the lumbosacral spinal cord in rats.MethodsMale adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed in SG neurons from isolated spinal cord slice preparations. IPSCs were recorded in individual SG neurons to which naftopidil (100μM), tamsulosin (100μM), silodosin (30μM), or prazosin (10μM) were applied sequentially with intervening washout periods. Strychnine (2μM), bicuculline (10μM), or tetrodotoxin (TTX)(1μM) were added before naftopidil. Individual outward currents were analyzed.ResultsThe bath application of naftopidil, yielded outward IPSCs in 13 of 52 SG neurons. The naftopidil response was unchanged in the presence of TTX. Regression analysis of the outward currents between the 1st and 2nd applications of naftopidil revealed a Pearson correlation coefficient of 0.996 with a line slope of 0.983. The naftopidil-induced outward current was attenuated in the presence of strychnine and/or bicuculline. The GABA/glycine-mediated outward currents induced by tamsulosin, silodosin, and prazosin were smaller than those obtained with naftopidil.ConclusionsNaftopidil-induced GABA/glycine-mediated outward currents in a subset of SG neurons prepared from the L6– S1 level of rat spinal cord. The results indicated that α1-adrenoceptor antagonists, particularly naftopidil, induce neural suppression (in part) by mediating hyperpolarization. The response is associated with glycinergic and/or GABAergic neural transmission. Naftopidil may suppress the micturition reflex and improve urinary storage symptoms as a subsidiary effect resulting from hyperpolarization in SG neurons of the spinal cord.

Effect of alpha1 adrenoceptor antagonist on lower urinary tract symptoms as a vasodilative agent

Effect of alpha1 adrenoceptor antagonist on lower urinary tract symptoms as a vasodilative agent

731 Effect of alpha-1 adrenoceptor antagonist and phosphodiesterase type-5 inhibitor on c-Fos and nerve growth factor expression in the central micturition areas: Hypertension associated rat model

731 Effect of alpha-1 adrenoceptor antagonist and phosphodiesterase type-5 inhibitor on c-Fos and nerve growth factor expression in the central micturition areas: Hypertension associated rat model

1524: Predictive Factors for the Effect of Alpha1-Adrenoceptor Antagonist on Subjective and Objective Parameters in Patients with Neurogenic Lower Urinary Tract Dysfunction: Special Focus on Alpha1-D/A Adrenoceptor ANT Agonist Naftopidil

You have accessJournal of UrologyPodium 44, Tuesday, May 22, 2007, 1:00 - 3:00 pm1 Apr 20071524: Predictive Factors for the Effect of Alpha1-Adrenoceptor Antagonist on Subjective and Objective Parameters in Patients with Neurogenic Lower Urinary Tract Dysfunction: Special Focus on Alpha1-D/A Adrenoceptor ANT Agonist Naftopidil Masayuki Takeda, Yukio Homma, Isao Araki, Hidehiro Kakizaki, Tomonori Yamanishi, Takashi Yokota, Momokazu Gotoh, Narihito Seki, Mineo Takei, Masaki Yoshida, Kimio Sugaya, Yasuhiko Lgawa, Osamu Nishizawa, and Japanese Naftopidil Neurogenic Lower Urinary Tract Dysfunction Study Group Masayuki TakedaMasayuki Takeda More articles by this author , Yukio HommaYukio Homma More articles by this author , Isao ArakiIsao Araki More articles by this author , Hidehiro KakizakiHidehiro Kakizaki More articles by this author , Tomonori YamanishiTomonori Yamanishi More articles by this author , Takashi YokotaTakashi Yokota More articles by this author , Momokazu GotohMomokazu Gotoh More articles by this author , Narihito SekiNarihito Seki More articles by this author , Mineo TakeiMineo Takei More articles by this author , Masaki YoshidaMasaki Yoshida More articles by this author , Kimio SugayaKimio Sugaya More articles by this author , Yasuhiko LgawaYasuhiko Lgawa More articles by this author , Osamu NishizawaOsamu Nishizawa More articles by this author , and Japanese Naftopidil Neurogenic Lower Urinary Tract Dysfunction Study Group More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31725-7AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1524: Predictive Factors for the Effect of Alpha1-Adrenoceptor Antagonist on Subjective and Objective Parameters in Patients with Neurogenic Lower Urinary Tract Dysfunction: Special Focus on Alpha1-D/A Adrenoceptor ANT Agonist Naftopidil." The Journal of Urology, 177(4S), p. 503 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 503 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Masayuki Takeda More articles by this author Yukio Homma More articles by this author Isao Araki More articles by this author Hidehiro Kakizaki More articles by this author Tomonori Yamanishi More articles by this author Takashi Yokota More articles by this author Momokazu Gotoh More articles by this author Narihito Seki More articles by this author Mineo Takei More articles by this author Masaki Yoshida More articles by this author Kimio Sugaya More articles by this author Yasuhiko Lgawa More articles by this author Osamu Nishizawa More articles by this author Japanese Naftopidil Neurogenic Lower Urinary Tract Dysfunction Study Group More articles by this author Expand All Advertisement PDF downloadLoading ...

Existence of Functional α1A- and α1D- but No α1B-Adrenoceptor Subtypes in Rat Common Carotid Arteries

Using the cannula inserting method, vasoconstrictor responses to alpha1-adrenoceptor agonists (noradrenaline [NA], phenylephrine [PE] and methoxamine [ME]) and effects of alpha1-adrenoceptor antagonists (WB4101, chloroethylclonidine [CEC] and BMY7378) were investigated in isolated and perfused rat common carotid arteries. The rank order of agonist potency and efficacy was NA = PE > ME. Either WB4101 or BYM7378 inhibited NA- and PE-induced constrictions in a dose-related manner. CEC did not inhibit the NA- and PE-induced responses. The ME-induced responses were also significantly blocked by either WB4101 or BMY7378. From these results, it is concluded that there are functional alpha1A- and alpha1D-adrenoceptor subtypes in rat common carotid arteries, but no functional alpha1B subtype.

Analysis of the effects of alpha 1-adrenoceptor antagonists on noradrenaline-mediated contraction of rat small mesenteric artery.

1. In this study, we examined the interaction between noradrenaline (NA) and phenylephrine (PE) with seven antagonists (prazosin, tamsulosin, phentolamine, WB-4101, 5-methylurapidil, spiperone and HV 723) in an attempt to characterize the alpha 1-adrenoceptor population of the rat isolated small mesenteric artery (SMA) preparation. 2. Six of the seven antagonists investigated produced concentration-dependent, parallel, rightward shift of the NA concentration-effect (E/[A]) curves. The exception was tamsulosin, which produced significant decrease of the upper asymptote. In the case of 5-methylurapidil and HV723, the Schild plot slope parameters were not significantly different from unity over the range of concentrations used. However, the Schild plot slopes obtained for the other antagonists were all significantly greater than unity, inconsistent with expectations for simple competitive antagonism. 3. HV723, prazosin and tamsulosin were also tested using PE as an agonist. All three antagonists produced concentration-dependent, parallel, rightward shifts of the PE curves and Schild analysis yielded slope parameters not significantly different from unity. The pKB estimates obtained for tamsulosin and prazosin were not significantly different from the pA2 values obtained when NA was used as agonist. In the case of HV723, the 95% confidence intervals for the pKB values yielded with NA and PE did not overlap (pKB = 8.80-9.13 and 8.15-8.77 for NA and PE, respectively). 4. In the absence of evidence to indicate that the steep Schild plots were due to failure to satisfy the basic criteria for quantitative analysis in a one-receptor system, we considered the possibility that the complexity was caused by an action of NA at inhibitory D1 receptors. The selective D1 receptor antagonists, SCH-23390 (10 nM), had no significant effect on the NA E/[A] control curve, but the apparent potency of 100 nM prazosin was reduced by approximately 3.5 fold. 5. This study indicates that the steep Schild plots obtained from the interaction between NA and alpha 1-adrenoceptor antagonists were due to the simultaneous activation of inhibitory D1 receptors by NA. Notwithstanding this complexity, our explanatory model of the system (see Appendix) suggests that the antagonist affinity values estimated in the absence of D1 receptor block were not significantly affected by this other action of NA. The low affinity estimate obtained for prazosin suggests that the pharmacologically-defined alpha IL-subtype operates in the SMA.