Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of endothelin-1 on the tone of the epididymal portion of the rat vas deferens were studied under treatment with drugs modulating the electrically evoked (single pulses, 1 msec, 80 V, 0.1 Hz) contractile responses. Endothelin-1 (0.01 nM-0.1 microM) concentration-dependently increased both the smooth muscle tone and the electrically stimulated contractions, the EC50 being 25.4 +/- 4.17 nM and 23.4 +/- 5.0 nM, respectively. The tonic contractions evoked by endothelin-1 persisted in the presence of 0.3 microM of tetrodotoxin or 10 microM of guanethidine. There were no significant differences in the EC50 values after tetrodotoxin (18.8 +/- 2.29 nM) or guanethidine (22.6 +/- 0.08 nM) as compared to controls, while the electrically stimulated contractile responses were completely inhibited. Clonidine (1, 3 or 10 nM) did not induce changes in the dynamic of the endothelin-1 effects on the tone. However, an increase in magnitude of the endothelin-1-induced contractions was observed on the background of the highest concentration of clonidine. Yohimbine, at concentrations of 1, 3 or 10 microM, significantly decreased the EC50 values for endothelin-1 to 16.4 +/- 1.02 nM, 16.1 +/- 1.60 nM and 8.09 +/- 1.15 nM, respectively. It is assumed that the development of the contractile effect of endothelin-1 on the tone of the electrically stimulated epididymal portion of the rat vas deferens does not depend on the integrity of the sympathetic innervation. However, a modulation of the endothelin-1 effects by yohimbine, rather than by clonidine, via postjunctional mechanisms, cannot be excluded.
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PMID:Drug-induced modulation of endothelin-1 effects on the tone of electrically stimulated rat vas deferens. 146 73

1. The relationship between endothelin-1(ET-1)-induced effects on the contractile responses of epididymal portion of rat vas deferens elicited by field electrical stimulation (FES: 80 V, 1 msec, 0.1 Hz) and the effects of the alpha 2-adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist yohimbine were studied. 2. ET-1 (0.01 nM-0.1 microM) concentration-dependently increased the FES-induced contractions. 3. ET-1 (0.1 nM-0.1 microM) reversed the inhibitory effect of clonidine on the FES-evoked contractions whereas ET-1 applied before clonidine exerted a dual effect on the clonidine-induced inhibition of the FES-evoked contractions. 4. The ET-1-induced enhancement of FES-induced contractions was potentiated in the presence of 1 microM yohimbine and was not observed at all in the presence of 10 microM yohimbine. Yohimbine, applied at concentrations of 1 and 10 microM exerted similar blocking effects on the alpha 1-adrenoceptor agonistic effects of phenylephrine. However, yohimbine at a concentration of 10 microM markedly potentiated the contractile effect of exogenous adenosine 5'-triphosphate (ATP), 30 microM. Tetrodotoxin abolished this effect of yohimbine. 5. The results presented here suggest the existence of modulating interactions between the ET-1-evoked increase of FES-induced contractions of rat vas deferens and the alpha 2-adrenoceptor drugs clonidine and yohimbine.
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PMID:Interactions between the effects of endothelin-1, clonidine and yohimbine on electrically-induced contractions in rat vas deferens. 151 61

The effects of the alpha-adrenoceptor agonist St-587 have been studied on the twitch responses induced by field stimulation in the prostatic portion of rat vas deferens. Moreover the drug's influence on the unstimulated prostatic and epididymal halves of rat vas deferens has also been determined. Alone and after addition of yohimbine (0.3 microM) it enhanced in a concentration-dependent manner the twitch responses in the prostatic half. Prazosin competitively antagonized (pA2 = 8.41 +/- 0.03) this effect. The enhancing effect of St-587 was not reduced in reserpinized animals. These results suggest that post-synaptic alpha 1-adrenoceptors are involved in the potentiation of twitch responses induced by St-587. When alpha 1-adrenoceptors were blocked by prazosin (0.1 microM), St-587 partially inhibited the twitch responses of the prostatic portion of rat vas deferens (Emax = 49.5 +/- 3.5%). Yohimbine completely reversed the inhibitory effects of both St-587 and clonidine. Furthermore St-587 antagonized the inhibitory effects of clonidine on twitch responses. Thus it appears that St-587 also behaves as a partial agonist of presynaptic alpha 2-adrenoceptors in this portion of rat vas deferens, but it did not induce contractions in the unstimulated prostatic half of the vas deferens. However, it competitively antagonized the alpha 1-adrenoceptor agonist phenylephrine by acting as an antagonist of prostatic postsynaptic alpha 1 adrenoceptors. These alpha 1-adrenoceptors are probably different from those that mediate the twitch enhancing response to St-587 in that portion. On the other hand, St-587 was a partial agonist of alpha 1-adrenoceptors in the epididymal half.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of St-587 on the alpha-adrenoceptors in the bisected rat vas deferens. 257 5

Verapamil (3 X 10(-6)-3 X 10(-5) M) enhanced the twitch contractions of the epididymal and prostatic portions of vas deferens stimulated at 0.1 Hz. This verapamil effect was essentially similar to those of diltiazem, D-600 and Bay K 8644. However, when stimulation at 2 Hz was used verapamil (3 X 10(-5) M) attenuated the contractions of the epididymal portion by half but still augmented those of the prostatic portion. Verapamil enhanced the reserpine- and prazosin-resistant component of the stimulation-induced contractions of both portions of the vas deferens. Yohimbine augmented the twitch response but attenuated the verapamil-augmented response. Verapamil did not augment norepinephrine- or tyramine-induced contractions whereas it augmented ATP-induced contractions of the prostatic portion but not of the epididymal portion. Verapamil increased the stimulation-evoked 3H-efflux from the vas deferens labelled with [3H]norepinephrine. It is suggested that verapamil augments non-adrenergic responses of both portions of the vas deferens by acting as a Ca agonist on the prejunctional site to increase the release of co-transmitter, or by acting on the postjunctional site to enhance the action of the substance released. Its effect in augmenting norepinephrine release is concluded not to contribute to the potentiating action.
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PMID:Verapamil enhances the non-adrenergic twitch response of rat vas deferens. 311 86

The interaction between amphetamine and clonidine on neurotransmission in the rat vas deferens was studied. In the whole vas deferens, clonidine 0.037 mumol/l displaced to the right the frequency-response curve evoked by either hypogastric or field stimulation. The frequency of stimulation that produced 50% of the maximal response (EF 50) was: control 4.0 Hz, clonidine 18.3 Hz (P less than 0.001 n = 4), for hypogastric nerve stimulation; and 2.1 Hz in controls and 17.1 Hz in clonidine-treated preparations, for field stimulation (P less than 0.001 n = 5). Preincubation with 5.4 mumol/l amphetamine antagonized the effect of clonidine (EF 50 amphetamine alone 6.2 Hz, amphetamine + clonidine 7.3 Hz; P greater than 0.5). After 12 min of incubation with clonidine 0.037 mumol/l the responses to 6.4 Hz (3 s, 0.5 ms) were decreased by 77 +/- 2.2%. Both yohimbine and amphetamine, in a concentration-dependent manner, attenuated the inhibition. Washout of clonidine produced a slow recovery of the responses. Inhibition of the motor response to nerve stimulation (6.4 Hz, 3 s) by 30 mumol/l 2',3'-cAMP was increased by 10 mumol/l dipyridamole and impaired by 100 mumol/l theophylline. Amphetamine, in a concentration that markedly reduced clonidine inhibition of neurotransmission failed to antagonize 2',3'-cAMP. In the bisected vas deferens clonidine inhibited the peak motor response to short trains of field stimuli in the prostatic portion ("non-adrenergic") and the sustained response in the epididymal portion ("adrenergic"). Yohimbine potentiated both types of responses and fully prevented the effect of clonidine. In the prostatic portion amphetamine slightly inhibited the peak motor response and attenuated the inhibitory effect of clonidine in both portions of the vas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amphetamine-clonidine interaction on neurotransmission in the vas deferens of the rat. 609 34

1 The proposal that dopamine activates a different population of receptors from those activated by noradrenaline and phenylephrine to cause contraction of the rat vas deferens has been investigated using a preparation of the epididymal half of this tissue. 2 In preparations preincubated in cocaine, oestradiol and propranolol, to block sites of amine loss and beta-adrenoceptors, noradrenaline was the most, and dopamine the least, potent of the three agonists. Phentolamine competitively inhibited each of the agonists to a similar extent. Prazosin also inhibited the actions of the three agonists to a similar extent. These results indicate that the three agonists activate a single population of alpha 1-adrenoceptors to cause contraction in this preparation. 3 In experiments using the prostatic half of the rat vas deferens, in the presence of cocaine, oestradiol, propranolol and prazosin, noradrenaline was approximately 40 times more potent than dopamine in causing inhibition of twitches induced by electrical field stimulation. Yohimbine competitively antagonized the effects of the two agonists to a similar extent indicating that both act at the same population of alpha 2-adrenoceptors. 4 Taken together, these findings do not lend support to proposals that there are populations of specific dopamine receptors located pre- and postjunctionally in the rat vas deferens.
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PMID:Dopamine acts at the same receptors as noradrenaline in the rat isolated vas deferens. 629 87

Our objective was to extend the study of age-related changes in the modulation of norepinephrine release by presynaptic alpha-2 adrenoceptors. The experimental model utilized was the epididymal and prostatic portion of the rat vas deferens, because the two portions differ in age-related changes and pattern of sympathetic neurotransmission. The functional influence of presynaptic alpha-2 adrenoceptors was evaluated by quantifying the potentiating effect of yohimbine on the contraction induced by transmural stimulation. Yohimbine-induced potentiation was much more pronounced in the epididymal portion of young rats and was reduced by aging only in this portion. Potassium-induced release of 3H-norepinephrine was significantly higher in the epididymal than in the prostatic portion, and an age-related reduction in 3H-norepinephrine release occurred only in the epididymal portion. However, aging did not change the inhibitory effect of clonidine on the contraction induced by transmural stimulation (0.2 Hz or single pulse) in either portion. Thus the age-related decline in alpha-2 feedback regulation is probably not directly related to changes in prejunctional alpha-2 adrenoceptor activity but may be associated with age-related changes in the amount of norepinephrine that stimulates this receptor. However, the lower overflow of neurotransmitter in the epididymal portion did not translate into age-related changes in the contractile responses to transmural stimulation (2-20 Hz). In the prostatic portion, aging increased the functional neurotransmission, partially because of a reduction in neuronal norepinephrine uptake. The results suggest that age-related changes are specific for each portion and may be associated with the pattern of neurotransmission of the tissue.
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PMID:Age-related changes in norepinephrine release and its modulation by presynaptic alpha-2 adrenoceptors in the rat vas deferens. 822 66

1. An involvement of imidazoline receptors in the modulation of neurotransmitter release was investigated in the prostatic portion of the rat vas deferens stimulated transmurally at 0.2 Hz or by single pulses. 2. Idaxozan and yohimbine induced a concentration-dependent potentiation of the contractile response to 0.2-Hz transmural stimulation in the epididymal and prostatic portion of the vas. 3. After reserpine treatment, idazoxan, but not yohimbine, still potentiated the contractile response, suggesting a possible involvement of imidazoline receptors. 4. Clonidine and rilmenidine, agonists with different affinities to alpha 2-adrenoceptors and imidazoline receptors, inhibited with the same potency the contractile responses to a single pulse transmural stimulation. 5. Yohimbine (a selective alpha 2-adrenoceptor antagonist) antagonized the inhibitory concentration effect curve to rilmenidine in a competitive manner. pA2 values for idaxozan (an antagonist to alpha 2-adrenoceptors and imidazoline receptors) were not different when noradrenaline or rilmenidine were used as agonists. Phenoxybenzamine blocked the effect of both agonists. 6. Thus, the potency relationship of agonists, as well as the effect of the antagonists, did not favor the hypothesis that imidazoline receptors are involved in the idazoxan-potentiating effect in the rat vas deferens.
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PMID:Are imidazoline receptors involved in sympathetic neurotransmission in rat vas deferens? 898 Oct 80

Inhibition of the field stimulation-induced twitch responses of the rabbit vas deferens by the muscarinic receptor agonist, McN-A-343, has been attributed to presynaptic muscarinic receptors of the M1 subtype located on noradrenergic nerve terminals. Stimulation of these receptors causes inhibition of transmitter release and inhibition of the contractile response. However, the selectivity of McN-A-343 for M1 receptors has been questioned and this throws doubt on whether the prejunctional receptors of the rabbit vas deferens are of the M1 subtype. In this study we have undertaken a comprehensive re-evaluation of the inhibition of prostatic and epididymal portions of the rabbit isolated field-stimulated vas deferens by several agonists, including McN-A-343, and quantified the antagonism by M1-selective antagonists, pirenzepine and telenzepine. Prostatic and epididymal portions of vasa deferentia from New Zealand White rabbits were immersed in a low Ca2+ Krebs solution at 32+/-0.5 degrees C gassed with 5% CO2 in oxygen. Yohimbine (1.0mM) was present throughout to block prejunctional alpha2-adrenoceptors. Field stimulation was applied by repeated application of single pulses (30 V, 0.05 Hz, 0.5 ms) and isometric contractions recorded. Carbachol and oxotremorine initially potentiated the epididymal contractions but at higher concentrations there was inhibition. In the prostatic portion, oxotremorine only inhibited. McN-A-343 produced inhibitory responses only in both epididymal and prostatic portions. Pirenzepine shifted the concentration-response curves forthe inhibitory responses to oxotremorine to the right. However, the potentiation of the twitches also became more apparent with the lower concentrations of oxotremorine. Schild plots for the antagonism by pirenzepine yielded pA2 values of 7.96+/-0.004 and 7.7+/-0.02 for the epididymal and prostatic portions, respectively. The concentration-response curves for the inhibition of twitches by McN-A-343 were displaced to the right in a parallel manner by pirenzepine in both prostatic and epididymal portions with no potentiation of the twitches. The Schild plot for this antagonism generated pA2 values of 7.68+/-0.01 and 8.07+/-0.01, respectively. Telenzepine caused parallel shifts of the McN-A-343 concentration-response curves to the right in prostatic portions, the pA2 value being 8.70+/-0.13. Telenzepine (10(-7) M) abolished the inhibitory effect of carbachol to reveal only concentration-dependent potentiation of the contractions. The Schild plot for antagonism of this contractile effect yielded a pA2 value (7.07+/-0.09) that was significantly less by almost two orders of magnitude (1.70) than the value for the antagonism by telenzepine of the McN-A-343-induced inhibitory response. The pA2 values of pirenzepine and telenzepine against the inhibitory responses of the rabbit vas deferens are consistent with the involvement of M1 receptors. This leads to the conclusion that McN-A-343 causes inhibition through this receptor type. The doubts concerning the selectivity of McN-A-343 for M1 receptors are therefore unfounded. The fact that McN-A-343 does not display a selective binding profile suggests that its selectivity does not arise from affinity differences but probably resides in its intrinsic efficacy.
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PMID:Inhibition of field stimulation-induced contractions of rabbit vas deferens by muscarinic receptor agonists: selectivity of McN-A-343 for M1 receptors. 1134 65