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)

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

1. The pharmacological characteristics of cloned mammalian alpha 1A/D-, alpha 1B- and alpha 1C-adrenoceptor subtypes expressed in rat 1 fibroblasts were determined in comparison to the binding and functional properties of these subtypes in rat tissues. 2. Analysis of [3H]-prazosin binding to membrane homogenates from rat 1 fibroblast cells expressing each of the alpha 1-subtypes indicated high affinity binding to a single population of binding sites. Binding affinities were similar for alpha 1A/D-, alpha 1B- and alpha 1C-subtypes (Kds: 0.13, 0.10 and 0.15 nM respectively) although a higher density of alpha 1B- and alpha 1C-receptors (Bmax: 4068 and 10,323 fmol mg-1 protein respectively) were expressed in comparison to alpha 1A/D (838 fmol mg-1). 3. Displacement of [3H]-prazosin from membranes expressing cloned alpha 1-adrenoceptor subtypes revealed that 5-methyl-urapidil, WB 4101, benoxathian and phentolamine displayed high affinity and selectivity for alpha 1A/D- over alpha 1B-subtypes. These compounds also had high affinity and selectivity for alpha 1C- over alpha 1B-subtypes. 5-Methyl-urapidil showed selectivity for alpha 1C (Ki 0.60 +/- 0.16 nM) over both alpha 1A/D (Ki, 9.8 +/- 2.8 nM) and alpha 1B (Ki 57.2 +/- 12 nM) subtypes. Prazosin and doxazosin were not subtype selective. 4. In comparison to [3H]-prazosin a similar pharmacological profile was obtained with [125I]-HEAT using cloned alpha 1A/D-, alpha 1B- and alpha 1C-adrenoceptors expressed in rat 1 fibroblasts. 5. The affinities of prazosin, WB 4101, 5-methyl-urapidil, phentolamine and benoxathian at cloned alpha 1A/D-receptors were consistent with alpha 1A affinities determined with chlorethylclonidine-treated rat cortical membranes. Affinities at cloned XIB-receptors were consistent with alpha 1B affinities determined with rat liver membranes.6. Using the epididymal rat vas deferens as a functional measure of alpha 1A affinity, prazosin (pA29.23 +/- 0.28), WB 4101 (pA2 9.58 +/- 0.12), phentolamine (pKB 7.90 +/- 0.16), benoxathian (pKB 9.21 +/- 0.21)and 5-methyl-urapadil (pKB 8.51 +/-0.16) were potent antagonists of noradrenaline-induced contractions.7. At present, evidence from cloning studies suggests the existence of at least three alpha 1-adrenoceptor subtypes. In contrast to the recent proposal for alpha l-adrenoceptor classification, the pharmacology of the cloned alpha 1A/D (or alpha lD)-adrenoceptor is more consistent with that of an alpha 1A-adrenoceptor characterized in rat cerebral cortex and vas deferens.
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PMID:Pharmacological properties of the cloned alpha 1A/D-adrenoceptor subtype are consistent with the alpha 1A-adrenoceptor characterized in rat cerebral cortex and vas deferens. 791 70

1. The alpha 1-adrenoceptor subtype mediating contraction of the rat hepatic portal vein to phenylephrine was characterized by use of competitive antagonists previously shown to have selectivity between the expressed alpha 1-subtype clones. Prazosin competitively antagonized the phenylephrine contractions with a pA2 value of 9.2, as did WB 4101 (pA2 9.4), 5-methyl urapidil (pA2 8.6), indoramin (pA2 8.4) and BMY 7378 (pA2 6.5). 2. The pA2 values on the rat portal vein correlated highly with their previously published pA2 values for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens and human prostate and poorly with those for the alpha 1B- and alpha 1D-adrenoceptors mediating contraction of the rat spleen and aorta, respectively. The antagonist pA2 values on the rat portal vein correlated highly with their previously published pK1 values for the expressed alpha 1a-clone and poorly with those for the expressed alpha 1b- and alpha 1d-clones. Therefore the results show that contraction of the rat portal vein to phenylephrine is mediated by alpha 1A-adrenoceptors. 3. The novel alpha 1-adrenoceptor antagonist RS 17053 had a relatively high affinity for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens (pA2 9.5) compared with the alpha 1B-adrenoceptors in the rat spleen (pA2 7.2) or the alpha 1D-adrenoceptors in the rat aorta (pKB 7.1), in agreement with its selectivity for the expressed alpha 1a-clone. However, RS 17053 had over 100 fold lower affinity for the alpha 1A-adrenoceptors mediating contraction of the rat portal vein (pKB 7.1) and human prostate (pKB 7.1) compared with its affinity for the alpha 1A-adrenoceptors in the rat epididymal vas deferens or the expressed alpha 1a-clone. 4. The difference in affinity of RS 17053 between the rat epididymal vas deferens and rat portal vein cannot be explained by a species difference in the receptor. Therefore RS 17053 may distinguish between subtypes of the alpha 1A-adrenoceptor in the rat portal vein and human prostate compared with those in the rat epididymal vas deferens or the expressed alpha 1a-clone.
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PMID:Different subtypes of alpha 1A-adrenoceptor mediating contraction of rat epididymal vas deferens, rat hepatic portal vein and human prostate distinguished by the antagonist RS 17053. 888 28

1 The subtypes of alpha1-adrenoceptor mediating contractions of rat vas deferens to endogenous and exogenous noradrenaline and to the exogenous agonists methoxamine, phenylephrine and A61603 have been examined. 2 The effects of antagonists on the shape of concentration-response curves, both tonic and phasic, to the four agonists were analysed. Prazosin produced parallel shifts in all cases. Particularly for RS 17053 against noradrenaline, there was some evidence for a resistant component of the agonist response. High concentrations of RS 17053 (1-10 microM) virtually abolished tonic contractions but phasic contractions were resistant. 3 A series of nine antagonists (the above and WB4101, benoxathian, phentolamine, BMY 7378, HV 723, spiperone) were investigated against contractions to noradrenaline. The correlation with the potency of the series of alpha1-adrenoceptor antagonists against contractions to noradrenaline was significant only for the alpha1A-adrenoceptor ligand binding site (r=0.88, n=9, P<0.01). 4 In epididymal portions (nifedipine 10 microM), the isometric contraction to a single electrical pulse is alpha1-adrenoceptor mediated. The correlation with ligand binding sites for 11 antagonists (the above plus ARC 239 and (+)-niguldipine) was significant only for the alpha1D-adrenoceptor subtype (r=0.65, n=11, P<0.05). 5 In conclusion, tonic contractions of rat vas deferens produced by exogenous agonists are mediated predominantly by alpha1A-adrenoceptors, although a second subtype of receptor may additionally be involved in phasic contractions. Nerve-stimulation evoked alpha1-adrenoceptor mediated contractions seem to predominantly involve non-alpha1A-adrenoceptors, and the receptor involved resembles the alpha1D-receptor.
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PMID:Investigation of the subtypes of alpha1-adrenoceptor mediating contractions of rat vas deferens. 1057 48

1. Frequency-response curves (0.1-30 Hz) were obtained in the epididymal portion of rat vas deferens. At low frequencies (0.1-1 Hz), the parameters evaluated were the first twitch and the fourth twitch at each frequency. The responses to trains of stimuli at intermediate (2-5 Hz) and high (10-30 Hz) frequencies were biphasic consisting of phase I (the first rapid phase of tetanus) and of phase II (the secondary slowly developing one). 2. Prazosin inhibited the first and the fourth twitch but not when the frequency was < 1 Hz. Suramin inhibited the first twitch while substantially depressing the fourth one. The combination of prazosin and suramin almost completely abolished all the twitches evoked by a train of stimuli at low frequencies. Nifedipine left almost unaltered the first twitch while markedly depressing the fourth one, especially at relatively high frequency (1 Hz). Verapamil was devoid of any inhibitory action. Papaverine depressed the first twitch while only at the highest concentration used (1 x 10(-4) M) markedly inhibited the fourth one. Chloroethylclonidine (CEC) depressed the first twitch and increased the fourth. 3. When intermediate (2-5 Hz) and high (10-30 Hz) frequencies are considered, prazosin and suramin partially inhibited both phase I and phase II, while in combination they almost completely abolished both phases. Nifedipine and verapamil selectively suppressed phase II, leaving phase I unaffected. Papaverine completely abolished both phase I and phase II. CEC was able to completely abolish phase I but increased phase II. 4. These results suggest that the response to the first twitch of a train at low frequency is prevailingly noradrenergic, prazosin-sensitive, while when the twitches are close enough (i.e. at 1 Hz) a summation of stimuli takes place and a predominant purinergic component, both suramin- and nifedipine-sensitive, becomes evident. 5. At high frequencies, both phases are due to the concomitant release of noradrenaline and adenosine triphosphate (ATP). The noradrenergic component of phase I is nifedipine-insensitive and CEC-sensitive, resembling the pharmacological profile of the endogenously released noradrenaline by single pulse, while that of phase II, nifedipine-sensitive and CEC-insensitive, is similar to that produced by exogenously applied noradrenaline.
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PMID:Differential effects of drugs interacting with autonomic transmitters on responses of rat vas deferens to field stimulation. 1109 47

The two portions of rat vas deferens differed in the postjunctional sensitivity to noradrenaline. Alpha1-adrenoceptor-linked phosphoinositide breakdown was analysed in this tissue. The noradrenaline-induced [3H]inositol phosphate accumulation was similar in both ends although the pEC50 was higher in the epididymal (5.97+/-0.07) than in the prostatic (5.47+/-0.15, P<0.01) portion. [3H]Prazosin showed similar density of binding sites in both portions. Tissue pretreated with pertussis toxin did not change [3H]inositol phosphate accumulation. Finally, Western blot analysis indicated a smaller concentration of Gq/11 protein in the prostatic half (-29+/-5%, P<0.01). These results suggest that the different sensitivity to noradrenaline could be due to the higher availability of this sort of G protein in the epididymal portion.
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PMID:Different alpha1-adrenoceptor-induced inositol phosphate formation in the two portions of rat vas deferens. 1119 28

The epididymal portion of the rat vas deferens produced prostaglandins (PG) E(2), F(2alpha)and 6-keto F(1alpha). Electrical stimulation (ES, 0.1 Hz, 1 ms) increased such production by 100%, and similar results were obtained in the presence of 1.0 microM bradykinin (Bk). When both stimuli were applied simultaneously, the increases in PG production were 1100% for PGE(2), 800% for PGF(2alpha)and 400% for PG6-keto F(1alpha). Prazosin abolished the effect of ES on PG production. A selective Bk B(2)-receptor antagonist abolished the increase in PG production induced by Bk, both in non-stimulated and in ES tissues. Bk (1.0 microM) elicited contractile responses in non-stimulated as well as in ES tissues, responses that were not modified in the presence of 10 microM indomethacin. In conclusion, the effects of Bk on prostaglandin production appears to depend on the activation of B(2) receptors, while the increase in prostaglandin release induced by ES, and the effects observed with both stimuli simultaneously, should be mediated by the release of noradrenaline and the subsequent activation of alpha(1) adrenoceptors.
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PMID:Bradykinin and electrical stimulation increase prostaglandin production in the rat vas deferens. 1148 2

We have characterized the expression of alpha1-adrenoceptor in epididymis from rats in different stages of sexual maturation: 40 (immature), 60 (young adult), and 120 (adult) days of age. Plasma testosterone levels were low in the immature animals but increased significantly in the 60- and 120-day-old animals. These changes were followed by a progressive increase in rat body weight and in caput and cauda epididymis relative weight. Reverse transcription polymerase chain reaction assay indicated that alpha1a-, alpha1b-, and alpha1d-adrenoceptor transcripts were present in both caput and cauda epididymis from adult rats. Ribonuclease protection assays further indicated that the expression of these alpha1-adrenoceptor transcripts differed with age and epididymal region analyzed. Prazosin (nonselective alpha1 antagonist), 5-methyl urapidil (alpha1A-selective), and BMY 7378 (alpha1D-selective) displaced [3H]prazosin binding curves in caput and cauda epididymis from 40- and 120-day-old rats. The potency order for these antagonists, as calculated from the negative logarithm of the inhibition constant (pK(i)) values for the high-affinity sites, indicated a predominant population of alpha1A-adrenoceptor subtype in caput and cauda epididymis from adult animals. Differences in pK(i) values in caput and cauda epididymis from immature and adult animals also suggested that the relative amount of alpha1-adrenoceptors, at the protein level, is modulated by sexual maturation. Taken together, the changes in alpha1-adrenoceptor expression during sexual maturation may suggest specific roles for these receptors in epididymal function.
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PMID:Alpha1-adrenoceptor subtypes in rat epididymis and the effects of sexual maturation. 1180 69

The aim of the present study is to evaluate whether paroxetine (a selective serotonin re-uptake inhibitor) can modify the contractile responses of isolated vas deferens. Some contractile agents, potassium chloride (KCl), adenosine 5'-triphosphate (ATP), noradrenaline (NA), and electrical field stimulation (EFS) caused contractions both in epididymal and prostatic portions of vas deferens. Paroxetine (PX) in concentrations 10(-7) and 10(-6)M potentiated the contractions to KCl and ATP only in epididymal portion but in higher concentrations (10(-5) and 10(-4)M) inhibited the responses in both portions. NA responses were inhibited by PX in all concentrations used, both in prostatic and epididymal portions. Prazosin (PR), an alpha adrenergic receptor blocking agent, inhibited PX-induced potentiation observed for higher concentrations of KCl. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion. Pretreatment with PX (10(-7) to 10(-6)M) increased the contractions to EFS but in 10(-5) and 10(-4)M concentrations inhibited them. Even though the preparations were washed out, the inhibited responses of contractile agents could not be restored. After a washout period for PX, when Bay K 8644 (calcium channel activator) was added to the bath medium, the contractile responses to KCl were partially restored. In calcium-free medium, KCl caused contractions in concentrations higher than 80 mM with lower amplitudes which were not affected by PX. Reserpinization did not change the inhibitory pattern of PX's effect on exogenously applied NA in all concentrations tested. In reserpinized rats, the potentiation caused by PX in exogenously applied ATP responses was not observed. In conclusion, we can say that PX has two different effects: inhibition and potentiation of contractions to various agonists. The inhibitory effect of the drug can be explained by a calcium channel blocking activity. The potentiating effect of the drug is mainly related to its presynaptic action, such as NA re-uptake inhibitory effect.
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PMID:The effects of paroxetine on rat isolated vas deferens. 1290 4

Chronic ethanol administration affects many organ systems, including sexual organs. One of these organs is the vas deferens whose contractility can also be altered by selective serotonin re-uptake inhibitors (SSRIs). The aim of the present study, is to evaluate whether paroxetine (PX), a SSRI, can modify the contractile responses of isolated vas deferens obtained from rats chronically treated with ethanol to the contractile agents, potassium chloride (KCl) and adenosine triphosphate (ATP). For 21 days, alcohol was applied with a modified liquid diet to sexually mature male Sprague-Dawley rats (200-240 g). The vas deferens of the rats were excised at the end of day 21 and suspended in the organ baths by classical pharmacological methods. The responses to contractile agents tested were decreased by chronic ethanol treatment in all groups compared to their untreated matches. PX (10(-7) and 10(-6)M) potentiated the contractions to KCl (20-180 mM) and ATP (10(-6) to 10(-3)M) in epididymal portion but its higher concentrations (10(-5) and 10(-4)M) inhibited the responses, both in the control and chronically ethanol treated rat groups. Prazosin (PR), an alpha adrenergic receptor blocker, could not inhibit PX-induced potentiation in lower concentrations of KCl but could inhibit the potentiation occurred at higher concentrations of KCl in epididymal portion both in the control and chronically ethanol treated rat groups. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion both in the control and chronically ethanol treated rat groups. In conclusion, all the results obtained in this study, suggest that chronic ethanol treatment decreased the contractility of vas deferens but did not alter the action pattern of PX on responses to KCl and ATP in rat vas deferens. On the other hand, the potentiation of responses to contractile agents induced by PX can be partially considered as the result of inhibition of noradrenaline re-uptake.
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PMID:Paroxetine alters KCl- or ATP-induced contractile responses of isolated vas deferens in rats chronically treated with ethanol. 1459 52


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