Journal of Smooth Muscle Research
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Volume 45 , Issue 4
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Review
Original
  • Eri Nakamura, Tsuyoshi Yokoi, Hiroyasu Fukuta, Takao Iida, Yasuo Tanak ...
    Type: Original
    Volume 45 (2009) Issue 4 Pages 149-166
    Released: September 26, 2009
    JOURNALS FREE ACCESS
    Effects of hypoxic solution (O2 tension, 161 ± 11 mmHg) on electrical responses of the membrane (slow waves), intracellular Ca2+-responses measured by Fura-2 fluorescence (Ca-transients) and isometric mechanical responses (phasic contraction) were observed in circular smooth muscles isolated from the guinea-pig stomach antrum. In normoxic solution (O2 tension, 362 ± 28 mmHg), muscle cells generated slow waves spontaneously, and switching to hypoxic solution caused an increase in frequency and decrease in duration of slow waves, with no significant change in the resting membrane potential. Hypoxia also reduced the amplitude and duration and increased the frequency of Ca-transients. The increase in frequency of slow waves by hypoxia was prevented by cyclopiazonic acid (CPA) but not by carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), potassium cyanide (KCN) or low-Ca solution. The reduction by hypoxia of the duration of slow waves was prevented by CCCP or KCN but not by CPA or low-Ca solution. Hypoxia resulted in an increase in frequency and decrease in amplitude of phasic contractions, and the changes were prevented by CPA but not by CCCP. These results suggested that in antrum smooth muscle tissues, the increase in frequency of spontaneous activity by hypoxia is related to the enhanced function of the CPA-sensitive internal Ca-stores in pacemaker cells, while the inhibition in amplitude of phasic contractions by hypoxia may be mainly related to the decrease in Ca2+ release from the CPA-sensitive internal stores in smooth muscle cells. It is concluded that in hypoxic solution, the function of internal Ca2+ stores is enhanced in ICC-MY and is inhibited in smooth muscle cells in the guinea-pig stomach antrum.
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  • Hiroyasu Fukuta, Makoto Koshita, Eri Nakamura, Hironori Nakamura, Atsu ...
    Type: Original
    Volume 45 (2009) Issue 4 Pages 167-185
    Released: September 26, 2009
    JOURNALS FREE ACCESS
    Effects of acupuncture treatment on mechanical responses produced by transmural nerve stimulation (TNS) and acetylcholine (ACh) were investigated in circular smooth muscle preparations isolated from the antrum of the stomach of genetically hyperglycemic rats. While control rats had blood glucose levels of about 140 mg/dl, this was approximately tripled in the genetically hyperglycemic rats, but only doubled in the acupuncture treated genetically hyperglycemic rats. Antrum smooth muscle produced phasic contractions spontaneously, with a similar frequency and amplitude in the three groups of rats. Effects of atropine and Nω-nitro-L-arginine (L-NA) on TNS-induced responses revealed that in the antrum smooth muscle of the control rats, cholinergic excitatory, non-adrenergic non-cholinergic excitatory (NANCE), nitrergic inhibitory and off-responses produced projections: the last projection was considered to be non-adrenergic non-cholinergic non-nitrergic (NANCNN) in nature. In genetically hyperglycemic rats, nitrergic and NANCNN projections were enhanced and NANCE projections were absent. Acupuncture treated genetically hyperglycemic rats showed a reduction of NANCNN projection and enhancement of cholinergic projection, with no alteration to nitrergic projection, but a recovery of NANCE projection. ACh elicited inhibitory responses at low concentrations (1-30 nM) and excitatory responses at high concentrations (100-300 nM), in the three groups of rats. L-NA converted the ACh-induced inhibitory responses to excitatory responses. Immunohistochemical examination indicated no significant difference in the distribution of c-Kit expressing cells in the antrum smooth muscle from the three groups of rats. The results indicated that in antral smooth muscle, hyperglycemia was associated with enhanced activity in nitrergic and NANCNN projections and attenuation of NANCE projections, and that acupuncture treatment caused both a reduced blood glucose level and attenuated NANCNN projections. In genetically hyperglycemic rats, cholinergic responses were enhanced by acupuncture, possibly due to the enhanced cholinergic projections, with no change in the sensitivity of postjunctional muscarinic receptors to ACh.
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  • Shinya Kobayashi, Yoshitaka Tomiyama, Kazuyasu Maruyama, Yuji Hoyano, ...
    Type: Original
    Volume 45 (2009) Issue 4 Pages 187-195
    Released: September 26, 2009
    JOURNALS FREE ACCESS
    Purpose: To compare the efficacy of the selective α1A-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against α-adrenoceptor agonist-induced contractions in mouse and hamster ureters. Methods: The four α1-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique. Results: In mouse ureters, silodosin (a selective α1A-adrenoceptor antagonist), doxazosin (a nonselective α1-adrenoceptor antagonist), terazosin (a nonselective α1-adrenoceptor antagonist), and alfuzosin (a nonselective α1-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pKB value) was silodosin (9.47 ± 0.16) > doxazosin (8.62 ± 0.15) > terazosin (8.39 ± 0.16) > alfuzosin (8.03 ± 0.12). In hamster ureters, all four antagonists shifted the phenylephrine concentration-response curve to the right, the rank order of potencies being silodosin (10.09 ± 0.13) > doxazosin (8.22 ± 0.16) > terazosin (7.75 ± 0.15) > alfuzosin (7.70 ± 0.10). In each case, silodosin was much more potent than the other three drugs. Conclusion: In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this α1A-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.
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