Neurogenic responses of urethra isolated from the dog

Hashimoto, Shigeki; Kigoshi, Shigeru; Muramatsu, Ikunobu

doi:10.1016/0014-2999(92)90240-5

Cited by 43 publications

(28 citation statements)

References 26 publications

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“…The application of prostaglandins, VIP, 5-HT or ATP did not mimic the relaxant response evoked by EFS in the pig lower urinary tract (Klarskov, 1988). Similarly, relaxation in the dog urethra was not affected by the presence of 5-hydroxytryptaminergic, histaminergic or purinergic blocking drugs (Hashimoto et al, 1992). Recently, the prolonged NO-independent relaxation in the pig urethra was investigated by using different 5-HT H1, H2 or GABAB receptor antagonists (Bridgewater & Brading, 1993).…”

Section: Discussionmentioning

confidence: 99%

Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation

Werkström

Persson

et al. 1995

British J Pharmacology

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1 Non-adrenergic, non-cholinergic (NANC) relaxations induced by electrical field stimulation (EFS) were studied in pig isolated urethra. The mechanism for relaxation was characterized by measurement of cyclic nucleotides and by study of involvement of different subsets of voltage-operated calcium channels (VOCCs). 2 EFS evoked frequency-dependent and tetrodotoxin-sensitive relaxations in the presence of propranolol (1 yM), phentolamine (1 pM) and scopolamine (1 pM). At low frequencies (< 12 Hz), relaxations were rapid, whereas at high (> 12 Hz) frequencies distinct biphasic relaxations were evoked. The latter consisted of a rapidly developing first phase followed by a more long-lasting second phase. 3 Treatment with the NO-synthesis inhibitor N0-nitro-L-arginine (L-NOARG; 0.3 mM) inhibited relaxations at low frequencies of stimulation. At high frequencies (> 12 Hz) only the first relaxation phase was affected. 4 Measurement of cyclic nucleotides in preparations subjected to continuous nerve-stimulation, revealed an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels from 1.3 ± 0.3 to 3.0±0.4 pmol mg'-protein (P<0.01). In the presence of L-NOARG, there was a significant decrease in cyclic GMP content to control. However, there was no increase in cyclic GMP content in response to EFS. Levels of cyclic AMP remained unchanged following EFS. 5Treatment with the N-type VOCC-inhibitor, wo-conotoxin GVIA (0.1 FM) reduced NO-dependent relaxations, the effect being most pronounced at low frequencies (1-4 Hz) of stimulation. The NOindependent second phase of the relaxation, studied in the presence of L-NOARG (0.3 mM) at 16-30 Hz, was however markedly reduced or abolished by w-conotoxin GVIA. w-Conotoxin MVIIC (1 pM) or w-agatoxin IVA (30 nM) had no effect on electrically evoked relaxations. 6 These results suggest that NANC-nerve derived urethral relaxation in the pig consists of two apparently independent components. One is mediated by NO and associated with an increase in cyclic GMP content. The other mediator is unknown and produces relaxations not associated with changes in levels of cyclic nucleotides. The release of this mediator seems to involve the N-type VOCC, since the relaxation was markedly reduced or abolished by w-conotoxin GVIA.

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Section: Discussionmentioning

confidence: 99%

Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation

Werkström

Persson

et al. 1995

British J Pharmacology

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“…2 ) [37,38], and contraction mediated via ␣ -ARs in the bladder base and urethra ( fig. 2, 3 ) [24,30,[39][40][41] . Although ␤ 2 -ARs were detected in the human bladder neck [42] , ␤ 3 -ARs predominated in the human bladder [43] .…”

Section: ␤ -Adrenoceptorsmentioning

confidence: 99%

Pharmacologic Targets on the Female Urethra

Canda

Çınar²,

Turna

et al. 2008

Urol Int

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Introduction: This article reviews the mechanisms affecting contraction and relaxation of the urethra in order to establish a basis for current and future treatments for urinary incontinence in women. Material and Methods: A review of the English literature using MEDLINE was performed between 1970 and 2008 on female urethra pharmacology, urinary incontinence, and mechanisms involved in contraction and relaxation of the female human urethra. Results: α-Adrenoceptors (ARs) cause contraction and β-ARs cause relaxation. Use of selective α-agonist and β-AR blocker agents might have potential for the treatment of stress urinary incontinence. Tolerable doses of cholinergic agonists did not have significant effects on intraurethral pressure. Nitric oxide seems to be the major nonadrenergic-noncholinergic inhibitory transmitter causing relaxation. c-kit-positive interstitial cells seem to regulate urethral tone. The roles of adenosine triphosphate and carbon monoxide have not been fully investigated in humans. Neuropeptides function similarly to the urinary bladder. Prostanoids cause urethral contraction and relaxation depending on their subtypes. Serotonin enhances the strength of urethral sphincteric contractions. The Rho-kinase pathway also appears to be modulating smooth muscle contraction in the urethra. Conclusions: Understanding of the urethral function and pharmacology may lead to the development of promising new agents which might be useful in the management of urinary incontinence in women.

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“…In another study in transverse urethral muscle strips of female dogs (with mucosa and connective tissue removed), 10 −7 M prazosin did not change a pronounced relaxation at 10-Hz electrosimulation [Hashimoto et al, 1993]. That prazosin reduces or abolishes contraction of the urethral sphincter is well established in animal studies [Chen and Brading, 1992;Hashimoto et al, 1992;Kakizaki et al, 1997] as well as in men [Ruutu et al, 1991;Tsujii et al, 1992] and women [Dwyer and Teele, 1992]. In men with urinary obstruction, prazosin has been shown to improve voiding [Ruutu et al, 1991] and in women it may cause incontinence [Dwyer and Teele, 1992].…”

Section: Discussionmentioning

confidence: 87%

In vitro electrostimulation-induced urethral relaxation in the guinea pig is blocked by prazosin

1999

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The purpose of this study was to characterize the electrostimulation‐induced relaxation in guinea pig urethral rings. From sacrificed male guinea pigs, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. The drop in baseline tension in response to electrical stimulation (rectangular pulses of 0.8‐msec pulse duration, a frequency of 3, 5, 10, and 20 Hz, and 75‐mA current) was measured in the presence of various pharmacologic agents. In urethral tissue precontracted with 10−5 norepinephrine, a significant relaxation of 34.8% was found at 10 Hz. This relaxation was not affected by the addition of neuropeptide Y (NPY, 10−8–10−6 M), 10−6 M atropine, 10−5 M α‐β‐methylene‐adenosine,5′‐triphosphate (α‐β‐methylene‐ATP, a purinergic antagonist), and tolazoline (α2 antagonist, 10−8–10−4 M). However, with the α−1 antagonist prazosin (5 × 10−8–5 × 10−7 M), no relaxation occurred. The tissue response was of neurogenic origin as it was blocked by 10−7 M tetrodotoxin. Norepinephrine‐precontracted urethral rings of male guinea pigs exhibit a relaxation response at 10 Hz that is α1‐adrenergic, non‐cholinergic, non‐purinergic, and independent of NPY. Neurourol. Urodynam. 18:33–39, 1999. © 1999 Wiley‐Liss, Inc.

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Neurogenic responses of urethra isolated from the dog

Cited by 43 publications

References 26 publications

Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation

Factors involved in the relaxation of female pig urethra evoked by electrical field stimulation

Pharmacologic Targets on the Female Urethra

In vitro electrostimulation-induced urethral relaxation in the guinea pig is blocked by prazosin

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