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)

Cholinoceptor agonists (arecoline congruent to carbachol greater than acetylcholine greater than pilocarpine) potentiated contractions to field stimulation of rat vas deferens via the activation of an atropine-sensitive muscarinic receptor. The potentiating effect of carbachol was dependent on the level of calcium in the medium, being more potent at higher calcium concentrations. The potentiating effect of carbachol was more pronounced in the epididymal than in the prostatic segment but was not attenuated by prazosin, an alpha 1-adrenoceptor antagonist. Carbachol did not significantly modify the direct contractile effects of noradrenaline nor alter the field-stimulation-evoked release of noradrenaline from the epididymal vas deferens. It is concluded that the potentiating effect of cholinoceptor agonists on the contractions to field stimulation in the rat vas deferens was not a result of an enhancement of adrenergic neurotransmission.
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PMID:Potentiation by cholinoceptor agonists of contractions to field stimulation of rat vas deferens. 299 23

The vas deferens of 14-54 d old rats was denervated, isolated after 7 d, divided into prostatic and epididymal halves, and denervation supersensitivity to noradrenaline, acetylcholine, methacholine and tetramethylammonium (TMA) was examined. The supersensitivity to any of these agonists did not appear in rats younger than 21 d of age. Thereafter a leftward shift of the dose-response curve and an increase in the maximum contraction to noradrenaline were observed. The maximum contraction became progressively greater with development in the prostatic half but was approximately constant in the epididymal half. Supersensitivity to methacholine distinctly developed with age in the epididymal half. Only a subsensitivity to TMA was observed, suggesting that TMA acts on the nerve. The effect of denervation on the response to acetylcholine in the epididymal half resembled that to methacholine, and in the prostatic half resembled that to TMA. The developmental change in the effect of denervation on noradrenaline was discussed in relation to the full contractile ability of the vas halves, and that to cholinergic drugs was discussed in relation to nicotinic and muscarinic receptor population.
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PMID:Post-natal change in the effect of denervation on the rat vas deferens. 639 86

1. The nature of muscarinic receptor subtypes in the isolated prostatic and epididymal segments of the vas deferens of the rat were studied. 2. Presynaptic receptors were characterized in segments under neurogenic transmural stimulation; postsynaptic receptors in segments without stimulation. 3. The present work suggests that the potency of ACh required to activate muscarinic receptors is higher in the prostatic than in the epididymal segment. 4. McN-A-343 was only able to induce dose-dependent contractions in the prostatic segment. 5. The pA2 value for 4-DAMP suggests that in the prostatic segment the postsynaptical ACh receptors seem to be pharmacologically similar to the ACh-M3 subtype. 6. Antagonism of the presynaptic ACh receptor subtype by pirenzepine supports the evidence that these receptors belong to the ACh-M1 subtype.
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PMID:Muscarinic receptor subtypes in the bisected vas deferens of the rat. 759 92

In the electrically field-stimulated rabbit vas deferens, muscarinic receptor agonists increase twitch-height by actions at postjunctional M2 receptors and decrease twitch-height by actions at prejunctional M1 receptors. In the present studies, in contrast to previous reports, muscarinic receptor agonists primarily decreased twitch-height, produced minimal increases in twitch-height, and, produced identical responses in both epididymal and prostatic tissue segments, thus permitting a more detailed investigation of the M1 receptor component of action of muscarinic receptor agonists in the rabbit vas deferens. The nonselective muscarinic receptor agonist carbachol produced biphasic effects on twitch-height in the vas deferens: lower concentrations increased twitch-height to only approximately 25-30% over control, whereas higher concentrations inhibited the twitch. The selective M1 receptor antagonist pirenzepine blocked the inhibitory effects of carbachol, and unmasked carbachol-induced increases in twitch-height. Atropine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) and AF-DX 116 (11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) blocked both the inhibitory and stimulatory effects of carbachol, but atropine and 4-DAMP were more potent in blocking the inhibitory than the stimulatory effects of carbachol, whereas the reverse was true for AF-DX 116. McN-A-343 (4-hydroxy-2-butynyl)trimethylammonium chloride, m-chlorocarbanilate) and 12 other muscarinic receptor agonists from a variety of chemical classes also produced concentration-dependent decreases in twitch-height. The log IC50s of the muscarinic receptor agonists for decreasing twitch-height were highly correlated with their log Kis for inhibiting [3H]pirenzepine (r = 0.96) and [3H]oxotremorine-M (r = 0.85) binding in rat hippocampal membranes. The present results demonstrate that the muscarinic M1 receptor mediating inhibition of twitch-height in the rabbit vas deferens has pharmacologic properties similar to the muscarinic M1 receptor in rat hippocampus.
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PMID:Muscarinic M1 receptor agonist actions of muscarinic receptor agonists in rabbit vas deferens. 845 95

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

The aim of the present study was to characterize the muscarinic acetylcholine receptor subtypes present in the caput and cauda of rat epididymis. The specific binding of [3H]quinuclidinyl benzilate ([3H]QNB) to epididymal membranes was time dependent, temperature dependent, and saturable. The cauda epididymis showed higher affinity to [3H]QNB and higher muscarinic receptor density when compared to the caput region. The [3H]QNB binding was tested in competition studies with different muscarinic receptor antagonists. Each antagonist tested displaced [3H]QNB bound to caput and cauda epididymal membrane with similar affinity. Correlation among the negative logarithm of inhibition constant values (pK(i)) for these antagonists obtained in the epididymis with their correspondent published pK(i) values obtained in tissues that expressed each receptor subtype (M1, M2, M3, and M4) indicated that the muscarinic receptors present in caput and cauda epididymis belong to the muscarinic M2 receptor subtype. When reverse transcription-polymerase chain reaction was used to identify muscarinic receptor mRNA subtypes in the epididymis, only m2 transcripts were detected in the caput region, while both m2 and m3 mRNA subtypes were observed in the cauda region. In conclusion, these results demonstrate that muscarinic receptors are present in the rat epididymis, with expression levels dependent on the region of the epididymis analyzed. Thus, the cholinergic neurotransmitter in the epididymis may be a factor controlling contractility and/or the luminal fluid microenvironment.
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PMID:Characterization of muscarinic acetylcholine receptors in the rat epididymis. 1156 33

Role of muscarinic receptor in the regulation of glucose uptake or lipolysis in adipose tissue remained unclear. In epididymal white adipose tissue (WAT) isolated from Wistar rats, we observed that acetylcholine (ACh) attenuated the insulin-stimulated glucose uptake and the release of glycerol from WAT in a concentration-dependent manner. Using the blockade of specific antagonists, both actions of ACh were characterized mainly due to an activation of M3 receptors. In the presence of various inhibitors for PLC-PKC pathway, ACh-decreased glucose uptake was also reversed. Taken together, these results suggest that muscarinic M3 receptor is involved in the regulation of glucose uptake and/or lipolysis in adipose tissue.
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PMID:Activation of muscarinic M-3 receptor may decrease glucose uptake and lipolysis in adipose tissue of rats. 1911 4