Effect of extracellular pH on contractile responses of the guinea-pig vas deferens

1. Effects of changing the pH of the bathing solution (7.0, 7.4 and 7.8) on the contractile response of the guinea-pig isolated vas deferens to ATP, noradrenaline (NA) and ATP in the presence of NA or electrical field stimulation (EFS) were investigated. 2. Low pH tended to augment the phasic contractile response to ATP (0.01-1 mmol/L), while high pH significantly reduced the contractile response to ATP. In contrast, low pH depressed the tonic contractile response to NA (0.1-10 mumol/L), while high pH augmented the response to NA. The contractile response to 1 mmol/L ATP was markedly potentiated in the presence of 0.1-10 mumol/L NA. The potentiated contractile response to ATP in the presence of NA was unaffected by changes in pH. 3. Electrical field stimulation produced a biphasic contractile response. Low pH enhanced the initial rapid phasic contractile response to EFS, while high pH depressed the response. In contrast, the second slow tonic contractile response to EFS was unaffected by changes in pH. 4. These findings may indicate that the phasic contractile response to EFS is mainly caused by ATP while the tonic contractile response is a synergistic response to ATP and NA concomitantly released from sympathetic nerve terminals.     

Effects of Thymoquinone,the Major Constituent of Nigella sativa Seeds,on the Contractile Responses of Rat vas Deferens

We have evaluated the effects of thymoquinone on smooth muscle contraction in the isolated rat epididymal vas deferens using tension recording technique. The contractile responses to norepinephrine (NE), KCl, and electrical field stimulation were recorded using an isometric transducer. Thymoquinone inhibited the contractile responses to exogenous NE (100?µM) and KCl (80?mM) in a concentration-dependent manner. Moreover, thymoquinone reduced the amplitude of electrically-evoked contraction of vas deferens in a concentration-dependent manner. Cumulative addition concentrations of CaCl₂ (0.1–10?mM) to tissue bath failed to increase the amplitude of contractile responses to electrical field stimulation in the presence of thymoquinone (80?µM). These results indicate that thymoquinone induced non-selective and concentration-dependent inhibition of contractile responses to NE, KCl, and electrical field stimulation. This action may be due to the ability of this alkaloid to interfere with the mobilization of Ca²⁺ required for smooth muscle contraction.     

Inhibitory effect of papaverine on the contraction induced by transmural stimulation in the isolated mouse vas deferens

The effect of papaverine on the contractions induced by adrenergic neurotransmission in the isolated mouse vas deferens was investigated. Papaverine, 10⁻⁷–10⁻⁵M, showed a dose-dependent and reversible inhibition on the induced contractions. When the frequency of stimulation was varied (2.5–20.0 Hz), the inhibitory effect tended to be marked at the lower frequencies.     

Effects of restraint stress on responsiveness of atria and vas deferens in Sprague–Dawley rats

1 The effects of stress in rats were evaluated by measuring changes in body weight and in responsiveness to noradrenaline (NA) in the isolated vas deferens and atria after the animals had been exposed to restraint or restraint and isolation. 2 Animals which were subjected to restraint alone (1 h day^?1 for 3, 7 or 28 days) had a significantly reduced rate of body weight gain. This effect was not potentiated by the additional stress of isolation. 3 Restraint alone did not produce significant changes in the responsiveness of the vas deferens to NA. However, adding isolation to restraint, as an additional stress, produced a further leftward shift of the NA dose–response curve for the vas deferens, so that there was a significant increase in sensitivity compared with control. 4 There was a significant rightward shift in the NA dose–response curves or reduction in sensitivity in the atria from animals which had been restrained for 7 or 28 days. Isolation did not produce a further rightward shift in the NA dose–response curve. 5 The results from this study indicate that the stress associated with repeated restraint reduces the rate of weight gain and reduces the responsiveness of the atria to NA. The responsiveness of the vas deferens to NA was increased by stress, but the combined effect of isolation and restraint was required to produce a significant effect. The differences in the effects of stress on these tissues could be associated with differences in presynaptic receptor populations.     

Effects of T-type calcium channel blockers and thalidomide on contractions of rat vas deferens

Background and purpose:

In rat vas deferens, nerve mediated-contractions to a single electrical stimulus consist of an early purinergic and a later adrenergic component with differing sensitivities to L-type calcium channel blockers. We have investigated the effects of the T-type calcium channel blockers mibefradil and (1S, 2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylic dihydrochloride (NNC 55-0396) against contractions in rat vas deferens. In addition, the actions of thalidomide were examined.

Experimental approach:

Prostatic and epididymal portions of rat vas deferens were stimulated with a single electrical stimulus every 5 min, and mouse whole vas deferens was stimulated with 40 pulses at 10 Hz every 5 min.

Key results:

Both mibefradil and NNC 55-0396 (100 µM) produced inhibition of contractions of epididymal portions (42 ± 13%, n= 7, and 43 ± 4%, n= 15, of control respectively). However, both agents produced small inhibitions of responses in prostatic portions, presumably by L-type calcium channel block. Thalidomide (100 µM) inhibited contractions in epididymal (55 ± 4% of control, n= 17) but not in prostatic portions of rat vas deferens. Thalidomide (10–100 µM) also inhibited contractions in mouse vas deferens.

Conclusions and implications:

The T-type calcium channel blockers mibefradil and NNC 55-0396 block particularly the adrenoceptor-mediated, nifedipine-resistant response to nerve stimulation in rat vas deferens, and this may suggest that this component involves T-type calcium channels. In addition, thalidomide has actions that resemble those of the T-type calcium channel blockers, in that it blocks nifedipine-resistant contractions in epididymal portions.     

氟西汀、氯丙咪嗪、文拉法新治疗抑郁症的成本-效果分析

目的：比较3种方案治疗抑郁症的经济效果和安全性。方法：运用药物经济学成本一效果分析对3种治疗方案进行分析评价。结果：氟西汀、氯丙咪嗪、文拉法新各组的治疗总成本，分别为28220元、25790．40元、55430．40元，有效率分别为85％、80％和87．5％，氯丙咪嗪组TESS得分显著及非常显著高于文拉法新及氟西汀组。结论：氟西汀组为最佳治疗方案。     

Comparison of corelease of noradrenaline and ATP evoked by hypogastric nerve stimulation and field stimulation in guinea-pig vas deferens

Contractions and overflow of tritium and ATP elicited by hypogastric nerve stimulation (HNS) and field stimulation (FS) were studied in the guinea-pig isolated vas deferens preincubated with [³H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique.HNS and FS elicited contraction, tritium overflow and ATP overflow. HNS at supramaximal current strength produced smaller responses than did FS at supramaximal current strength (210 pulses/7 Hz). Supramaximal HNS and submaximal FS were used in the remainder of the study. Prazosin (0.3 mol/l) reduced contractions and the overflow of ATP elicited by both HNS and FS; the evoked overflow of tritium was not changed (210 pulses/7 Hz). Combined administration of prazosin (0.3 mol/l) and suramin (300 mol/l) abolished contractions and reduced the overflow of ATP elicited by both HNS and FS slightly more than did prazosin alone; tritium overflow again was not changed (210 pulses/7 Hz). Contractions, tritium overflow and ATP overflow increased with the frequency of both HNS and FS (from 7 to 25 Hz; 210 pulses); the increase in ATP overflow with frequency was more marked than the increase in tritium overflow. The preferential increase of ATP overflow with the frequency of HNS and FS persisted in the combined presence of prazosin (0.3 mol/l) and suramin (300 mol/l).The study confirms for HNS, a more physiologic way of sympathetic nerve stimulation, several observations previously obtained with FS. First, HNS-evoked ATP release is detectable as an overflow of ATP into the superfusion fluid. Second, a large part of the HNS-evoked release of ATP is postjunctional in origin, due to activation of post-junctional ₁-adrenoceptors and presumably P₂-purinoceptors. Third, the average neural release of ATP per pulse facilitates with the frequency of stimulation to a greater extent than the average release of noradrenaline per pulse.     

Evidence for the participation of calcium in non-genomic relaxations induced by androgenic steroids in rat vas deferens

BACKGROUND AND PURPOSE: Androgens cause non-genomic relaxation in several smooth muscle preparations. However, such an effect has not been investigated in rat vas deferens yet. Our purpose was to study the effect of testosterone and derivatives in this tissue. EXPERIMENTAL APPROACH: The influence of androgens was tested on contraction and translocation of intracellular Ca(2+) induced by KCl in rat vas deferens in vitro. KEY RESULTS: The testosterone derivative 5alpha-dihydrotestosterone produced a rapid and reversible concentration-dependent relaxation of KCl-induced contractions. Other androgens were also effective, showing the following rank order of potency: androsterone >5beta-dihydrotestosterone >androstenedione >5alpha-dihydrotestosterone >testosterone. Calcium-induced contractions were also inhibited (about 45%) by 5alpha-dihydrotestosterone (30 microM). Moreover 5alpha-dihydrotestosterone blocked the increase of intracellular Ca(2+) induced by KCl, measured by the fluorescent dye fura-2. Relaxation to 5alpha-dihydrotestosterone was resistant to the K(+) channel antagonists glibenclamide, 4-aminopyridine and charybdotoxin. It was not affected by removal of epithelium or by L-NNA (300 microM), an inhibitor of nitric oxide biosynthesis, nor by selective inhibitors of soluble guanylate cyclase, ODQ or LY 83583, indicating that nitrergic or cGMP mediated mechanisms were not involved. The androgen-induced relaxation was also not blocked by the protein synthesis inhibitor cycloheximide (300 microM) or by the classical androgen receptor flutamide (up to 100 microM), corroborating that the effect is non-genomic. CONCLUSIONS AND IMPLICATIONS: Testosterone derivatives caused relaxation of the rat vas deferens, that did not involve epithelial tissue, K(+) channels, or nitric oxide-dependent mechanisms, but was related to a partial blockade of Ca(2+) influx.     

α1‐ and α2‐Adrenoceptor hyporesponsiveness in isolated bisected vas deferens of bile duct‐ligated rats

1 It has been suggested that cholestasis accompanied with changes in autonomic balance and hyporesponsiveness in muscarinic and adrenergic receptors of some organs, e.g. cardiovascular system. Increased plasma levels of epinephrine and norepinephrine has been shown during cholestasis suggesting augmented activity of sympathetic nervous system. In this study we evaluate both α₁ and α₂ responsiveness in isolated rat vas deferens, as a tissue with rich adrenergic innervations. 2 Epididymal and prostatic halves of vas deferens responsiveness have been studied to phenylephrine and clonidine respectively in three groups of un‐operated, sham‐operated (sham), and bile duct‐ligated (BDL) rats. 3 Our results indicate that in vas deferens of BDL animals, the concentration‐response curve of both phenylephrine and clonidine shifted to rightward compared to control group, while the position of concentration‐response curve of sham group did not change significantly (P > 0.05). EC₅₀ of phenylephrine and IC₅₀ of clonidine were increased showing a decreased responsiveness of tissue to phenylephrine (P < 0.05) and clonidine (P < 0.001) in BDL rats. 4 In this study, both subtype of α‐adrenoceptors (α₁ and α₂) has been studied in cholestatic rat vas deference. Our results showed that cholestasis induce hyporesponsiveness to phenylephrine and clonidine. These results are consistent with previous reports, suggesting the hyporesponsiveness of α₁‐adrenoceptors in pulmonary artery and papillary muscle and mesenteric beds. Our conclusion is that the cholestasis induces hyporesponsiveness to phenylephrine and clonidine in epididymal (α₁‐adrenoceptors) and prostatic (α₂‐adrenoceptors) halves of rat vas deferens respectively. Although the logical explanation to this hyporesponsiveness is the down regulation but it has been suggested that it is not because of down regulation.     

爱普列特对原代培养大鼠输精管上皮细胞及bcl-2表达的影响

目的　探讨爱普列特对原代培养SD大鼠输精管上皮细胞及原癌基因bcl 2表达的影响。方法　应用HE染色、电镜、流式细胞术和免疫组化方法研究爱普列特对输精管上皮细胞形态改变、细胞凋亡率以及bcl 2表达的影响。结果　 0 1 μmol·L- 1 爱普列特对细胞形态无显著影响 ;0 3和 1 0 μmol·L- 1 爱普列特作用 72h后 ,细胞呈核固缩、深染、碎裂、染色质边集等多种形态改变 ,电镜下可见典型的凋亡细胞特征 ;流式细胞仪分析结果显示 ,溶剂对照组细胞凋亡率为 3 42 %± 1 49% ,0 1、0 3和 1 0 μmol·L- 1 爱普列特作用 72h后 ,细胞凋亡率分别为 4 66 %± 2 2 3 % ,39 0 4 %± 1 0 69%和 52 74%± 8 91 % ;免疫组化结果显示输精管上皮细胞bcl 2阳性率为 76 96 %± 9 2 5 % ,0 1、0 3和 1 0 μmol·L- 1 爱普列特作用 72h后 ,Bcl 2阳性表达的百分率分别为 63 93 %± 3 40 %、52 82 %± 8 66 %和 2 9 64 %± 8 74%。结论　 0 1 μmol·L- 1 爱普列特对大鼠输精管上皮细胞无影响 ,0 3和 1 0 μmol·L- 1 可诱导大鼠输精管上皮细胞发生凋亡 ,其作用机制可能与降低bcl 2表达有关     

The effects of chronic reserpine treatment on the contractile activity of the isolated vas deferens of the guinea pig.

Chronic reserpine treatment of guinea pigs during 5 days (1 mg/kg/day) induces postjunctional supersensitivity in the isolated vas deferens. It has been previously proposed that postjunctional supersensitivity occurs as a result of an ionic and/or membrane mechanism. Contrasting with previous observations in vascular smooth muscle the present results demonstrate that chronic reserpine treatment did not increase the sensitivity of the depolarized vas deferens to calcium. Experiments on drug responsiveness show that the supersensitive depolarized tissues have a greater and slower rate of loss of responsiveness than do control vasa deferentia. However, in a Ca2+-free Krebs solution responsiveness of supersensitive vasa deferentia did not differ from that of control tissues. These findings suggest that, in the guinea-pig vas deferens, reserpine-induced supersensitivity could be at least partially dependent on the increased availability of a calcium store(s) probably located at the cell membrane and/or cytoplasmic compartments.     

Nature of neuronal uptake and noradrenaline--adrenaline effects in the isolated rat vas deferens.

Uptake mechanisms in the rat vas deferens have not yet been thoroughly investigated. In this study we show that uptake inhibition by cocaine, amantadine and desmethylimipramine induces increases in sensitivity that are greater for adrenaline than for noradrenaline. However, this does not occur when guanethidine is used. These results are clearly in disagreement with the neuronal uptake hypothesis. Uptake mechanisms in the rat vas deferens may be different from those of other tissues.     

Replacement of K+ with Rb+ or Cs+, and its effects on the mechanical responses to norepinephrine and methacholine in the rat vas deferens

The rat vas deferens was stored overnight in cold, K⁺-free Krebs solution to deplete intracellular K⁺ then incubated in K⁺-, Rb⁺- or Cs⁺-containing Krebs solution at 37°C to load these ions inside the cells. After 4 h, the contents of K⁺ or Rb⁺ reached the level of K⁺ in the fresh vas deferens; the content of Cs⁺ was less than half that of the fresh vas deferens. Dose-response curves to norepinephrine and methacholine were determined under these conditions, and the curves in Rb⁺ or Cs⁺ solution were compared with those in K⁺ solution. The cold storage per se had little effect on the dose-response curves in K⁺ solution except that it slightly decreased the maximal response to norepinephrine. The dose-response curves in Rb⁺ solution were to the left of those in K⁺ solution. The maximal response to methacholine was greatly increased. On the other hand, the dose-response curves in Cs⁺ solution were to the right of those in K⁺ solution. The maximal responses were greatly decreased with both drugs. The results suggest that Rb⁺ but not Cs⁺ can fully substitute for K⁺ in the rat vas deferens response to norepinephrine and methacholine.     

Mechanisms of the release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens

Summary In the rat vas deferens, DMPP is a substrate of uptake, (K_rn = 11.5 mol/I). After block of vesicular uptake, monoamine oxidase and catechol-O-methyl transferase, after loading of the tissue with ³H-noradrenaline, and in calcium-free solution (i. e., when axoplasmic ³H-noradrenaline levels were high and when depolarization-induced exocytotic release was impossible), DMPP induced a pronounced outward transport of ³H-noradrenaline. On the other hand, when, in similar experiments, vesicular uptake and monoamine oxidase were intact (i.e., when axoplasmic ³H-noradrenaline levels were low), DMPP induced very little outward transport of ³H-noradrenaline. This discrepancy indicates that DMPP has little ability to mobilize vesicularly stored ³H-amine.When the medium contained calcium (catechol-O-methyl transferase inhibited, all other mechanisms intact), 100 (but not 10) mol/l DMPP induced a hexamethonium-sensitive release of ³H-noradrenaline of short duration. Hence, in the presence of extracellular calcium, 100 mol/l DMPP elicits exocytotic release via activation of hexamethonium-sensitive nicotinic acetylcholine receptors.DMPP inhibits the monoamine oxidase of rat heart homogenate with an IC₅₀ of about 100 mol/l.Abbreviations COMT catechol-O-methyl transferase - DMPP dimethylphenylpiperazinium - DOMA dihydroxymandelic acid - DOPEG dihydroxyphenylglycol - MAO monoamine oxidase - NMN normetanephrine - OM-fraction column chromatographic fraction containing all O-methylated ³H-metabolites - OMDA fraction containing O-methylated and deaminated metabolites Supported by the Deutsche Forschungsgemeinschaft (SFB 176) Send offprint requests to U. Trendelenburg at the above address     

Attenuation of contractility in rat epididymal vas deferens by Rho kinase inhibitors

The involvement of Ca(2+) sensitization mediated through Rho kinase in the contractility of rat epididymal vas deferens was investigated using Rho kinase inhibitors, trans-4-[(1R)-1-aminoethyl]-N-4-pyridinilcyclohexanecarboxamide dihydrochloride (Y-27632) and 1-(5-isoquinolinesulphonyl)homopiperazine (HA 1077), in comparison with myosin light chain kinase (MLCK) inhibitors, wortmannin and 1-(5-chloronaphthalenesulphonyl)homopiperazine (ML-9) and agents that affect protein kinase C (PKC) and non-receptor tyrosine kinase intracellular signalling. 2 In Ca(2+)-free/ethyleneglycol-bis-(beta-aminoethylether)N,N,N('),N(')-tetraacetic acid (EGTA) (1 mM) medium, noradrenaline evoked sustained contractions. Y-27632 and HA 1077 caused a concentration-dependent inhibition and complete relaxation (IC(50), 1.08 and 1.75 microM respectively). The Ca(2+)-free contraction was reduced by wortmannin (10 microM) or ML-9 (10 microM) but not by inhibitors of diacylglycerol metabolism, 3-[2-[4[bis(4-Fluoropheny)methylene]-1-piperidinyl]-2,3-dihydro-2-thioxi-4(H)-quinazolinone (R59949) (10 microm) or 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) (10 microM) or by the phospholipase A(2) (PLA(2)) inhibitor, quinacrine (up to 100 microM) or tyrosine kinase inhibitor, genistein (30 microM). 3 In the presence of Ca(2+) (2.5 mM), noradrenaline (100 microM) evoked rhythmic activity and biphasic tonic contractions. Y-27632 (1-10 microM) or HA 1077 (1-10 microM) reduced the amplitude of rhythmic activity and tonic contractions. ML-9 (10 microM) attenuated the occurrence of rhythmic activity and modestly reduced the tonic contractions. ML-9 (10 microM) combined with Y-27632 (10 microM) significantly reduced the tonic contractions. ML-9 (30 microM) alone (or combined with Y-27632 10 microM) suppressed the rhythmic activity and substantially reduced (or abolished) the tonic contractions. 4 Contractions evoked by high [K(+)](o) (120 mM) or alpha,beta-methylene ATP (10 microM) were reduced significantly by Y-27632 (1-3 microM) indicating that the Rho kinase signalling pathway is activated by direct tissue depolarization or by stimulation of ligand-gated P(2X) purinoceptors. 5 Collectively, these results indicate that Ca(2+)-sensitization mediated by Rho kinase is involved in agonist- or depolarization-induced contraction of rat epididymal vas deferens. It is the major contractile mechanism underlying noradrenaline-induced Ca(2+)-free responses. It contributes to Ca(2+)-dependent rhythmic contractility and optimizes the development of full contractile tension triggered through calmodulin/MLCK activation by stimulated influx of Ca(2+).     

Panic disorder. A long‐term treatment study: fluoxetine vs imipramine

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and imipramine in the acute and long‐term treatment of panic disorder in 38 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. On the basis of HRSA mean scores evaluation, fluoxetine was found to be quicker than imipramine in reducing generalized anxiety at the end of the first week of treatment. However, through PASS and CGI mean scores evaluation, no statistically significant differences were found at any time in the efficacy of fluoxetine and imipramine on the total number of panic attacks, anticipatory anxiety or phobia severity. Fluoxetine has also turned out to be better tolerated than imipramine and to be effective at dosages low enough to avoid the event of an activation syndrome. Long‐term evaluation has shown high rates of persistent remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

Studies on the inhibitory action of somatostatin in the electrically stimulated rat vas deferens.

Somatostatin (SS) inhibits in a dose-dependent manner electrically evoked contractions in the rat vas deferens. This action was not modified by yohimbine, naloxone or a mixture of antagonists containing atropine, phentolamine, methysergide, burimamide, propranolol and indomethacin, but was markedly potentiated by reducing the Ca2+ concentration of the medium from 2.5 to 1.25 mM and greatly inhibited when increasing the Ca2+ concentration of the medium from 2.5 to 5.0 mM. Clonidine (CLO), but not beta-endorphin (ENDO) was affected similarly to SS by changing the Ca2+ concentration of the medium. The contractile effect of norepinephrine in unstimulated rat vas deferens was not altered by SS. These results were taken as an indication that SS produces its inhibitory action in the rat vas deferens by interacting with specific SS and its receptors presumably located in the cell membranes of adrenergic nerve terminals. The interaction between SS and its receptors may provoke a decreased diffusion of Ca2+ ions into the nerve terminals and/or a decreased mobilisation of Ca2+ ions from intraneuronal stores thus leading to a reduction in electrically evoked release of norepinephrine.     

Effects of carbenoxolone on syncytial electrical properties and junction potentials of guinea-pig vas deferens

The effects of the putative gap junction blocker carbenoxolone on smooth muscle syncytial properties and junction potentials were studied in guinea pig vas deferens (GPVD). Treatment with 50 μM carbenoxolone reversibly and significantly increased input resistance (R _in) (by 682.5 ± 326.0 %, P < 0.05) and abolished cable potentials within 6–7 mins of incubation, without disturbing resting membrane potential. Carbenoxolone reversibly and significantly increased the amplitude of spontaneous excitatory junction potentials (sEJPs) by 96.9 ± 35.45% (P < 0.05), shifted their amplitude distribution rightwards, and reduced their frequency of occurrence by 58.17 ± 17.7% (P < 0.05), without altering their time courses. Similarly, carbenoxolone increased the amplitude of evoked excitatory junction potentials (eEJPs) by 17.7 ± 5.88% and τ _decay by 19.43 ± 8.29% (P < 0.05). Our results indicate that carbenoxolone alters the electrical properties and junctional potentials of the GPVD by a mechanism consistent with a relatively specific block of gap junctions. These results suggest that gap junction mediated cell-to-cell communication may significantly modulate the electrical properties and junctional potentials of the GPVD and consequently the physiological functioning of this tissue.     

Differential effects of pinacidil,cromakalim,and NS 1619 on electrically evoked contractions in rat vas deferens

目的：本文研究新近研制的ＡＴＰ敏感性钾通道开放剂，吡那地尔（Ｐｉｎ）和ｃｒｏｍａｋａｌｉｍ（Ｃｒｏ），以及钙离子激活性钾通道开放剂ＮＳ１６１９对电场刺激所致大鼠输精管收缩的作用．方法：利用电场刺激（０．３Ｈｚ，１ｍｓ，６０Ｖ）反复性引致输精管单相性收缩．结果：Ｐｉｎ和Ｃｒｏ浓度依赖性减低电刺激收缩．格列本脲（Ｇｌｉ）而非ｃｈａｒｙｂｄｏｔｏｘｉｎ拮抗上述两药的舒张作用．Ｐｉｎ右移去甲肾上腺素的浓度－收缩曲线，同时降低最高收缩反应．Ｇｌｉ抵消Ｐｉｎ的作用．Ｃｈａｒｙｂｄｏｔｏｘｉｎ而非Ｇｌｉ减低ＮＳ１６１９的平滑肌舒张作用．结论：ＡＴＰ敏感性和钙离子激活性钾通道参与调节输精管平滑肌的收缩性．     

Autoradiographic study of the rat vas deferens incubated with 3H-noradrenaline

Summary Rat vasa deferentia were incubated with 0.2 mol/l ³H-noradrenaline for 60 min and then washed out with amine-free solution for 100 min. Autoradiography then revealed a preferential labelling of the varicosities in the immediate vicinity of the surface of the tissue. However, when tissues were obtained from reserpine-and pargyline-pretreated rats (to block vesicular uptake and monoamine oxidase), ³H-noradrenaline was able to penetrate more deeply into the tissue. These differences are in accordance with the view that the autoradiographs reflect the ³H-noradrenaline concentration gradient (within the extracellular space) generated by the neuronal uptake of the 3H-amine; the concentration gradient is steeper (and the heterogeneity of labelling is more pronounced) in tissues with intact vesicular uptake and monoamine oxidase than in tissues in which these mechanisms had been inhibited.Send offprint requests to I. Azevedo at the above adress