Are imidazoline receptors involved in sympathetic neurotransmission in rat vas deferens

• 1.1. 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.
• 2.2. 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.
• 3.3. After reserpine treatment, idazoxan, but not yohimbine, still potentiated the contractile response, suggesting a possible involvement of imidazoline receptors.
• 4.4. Clonidine and rilmenidine, agonists with different affinities to α₂-adrenoceptors and imidazoline receptors, inhibited with the same potency the contractile responses to a single pulse transmural stimulation.
• 5.5. Yohimbine (a selective α₂-adrenoceptor antagonist) antagonized the inhibitory concentration effect curve to rilmenidine in a competitive manner. pA₂ values for idaxozan (an antagonist to α₂-adrenoceptors and imidazoline receptors) were not different when noradrenaline or rilmenidine were used as agonists. Phenoxybenzamine blocked the effect of both agonists.
• 6.6. 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.

     

The effects of castration on neurotransmission in the rat vas deferens

1 Responses to adrenoceptor agonist drugs and to field stimulation were examined in vasa deferentia from adult castrated or intact rats. Isometric tension was recorded in vitro from whole or transversely bisected vasa. 2 After castration vasa exhibited spontaneous contraction, noradrenaline no longer produced a 'tonic' contraction but increased the 'phasic' spontaneous activity and salbutamol inhibited spontaneous activity by a beta-adrenoceptor-mediated mechanism. 3 After castration the 'adrenergic' components of the contractile responses to field stimulation were lost whereas 'non-adrenergic' responses remained, pre-junctional inhibition of field stimulation-induced contractions by either endogenous or exogenous activation was lost but adrenergic terminals could still be demonstrated microscopically. 4 Testosterone treatment partially reversed these effects of castration. 5 The relevance of these results to the nature of neurotransmission and to the genesis of spontaneous contraction in the vas deferens is discussed.     

突触前组胺H_1和H_3受体对豚鼠输精管交感神经冲动传递的影响(英文)

(R)-α-甲基组胺(α-MeHA)低浓度抑制,高浓度增强电场刺激诱发的离体输精管收缩。上述效应可分别被thioperamide和氯苯那敏拮抗,Pyridelethyl-amine(Pyr)能增强电场刺激诱发的输精管收缩,α-MeHA和Pyr对于直接电刺激或去甲肾上腺素(NE)诱发的输精管收缩均无影响,以上表明,豚鼠输精管交感神经末稍分布有组胺H_3和H_1两种受体,它们分别介导抑制和促进NE的释放。     

Angiotensin effects on vas deferens adrenergic and purinergic neurotransmission

Angiotensin effects on purinergic and adrenergic neurotransmission in the rabbit vas deferens were examined. Both angiotensins inhibited the non-adrenergic, and potentiated the adrenergic, neurogenic contraction. Angiotensin III inhibited the non-adrenergic neurogenic contraction to a greater extent than angiotensin II at all concentrations tested (maximal inhibition being 42 +/- 4 vs. 17 +/- 3% for angiotensin II). Angiotensin II was more potent than angiotensin III at potentiating adrenergic neurotransmission. Neither peptide altered the postjunctional action of either putative neurotransmitter, ATP or norepinephrine. These results are inconsistent with the hypothesis that ATP and norepinephrine are released in constant ratios. Furthermore, the different pattern of angiotensin responses is consistent with the existence of at least two separate angiotensin receptors with markedly different affinities for angiotensin II and angiotensin III.     

A comparison of the effects of oxodipine and nifedipine on rat vas deferens

The effects of oxodipine, a new dihydropyridine, were studied and compared with those of nifedipine in the complete vasa deferentia and in the prostatic and epididymal halves of the rat vas deferens. Oxodipine and nifedipine, 10(-9) -10(-6)M, produced a dose-dependent inhibition of the contractile responses induced by single pulse stimulation, noradrenaline (3 x 10(-5)M) and high-K (50 mM). The inhibitory effects of oxodipine were significantly reduced in high Ca media. From these experiments it is concluded that oxodipine, like nifedipine, produced a similar and potent inhibitory effect of the contractile responses induced in the rat vas deferens.     

Amphetamine-clonidine interaction on neurotransmission in the vas deferens of the rat

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)     

A comparison of the effects of nifedipine and verapamil on rat vas deferens.

Nifedipine preferentially blocks contractions of the prostatic end of the rat vas deferens to single pulse field stimulation, leaving the epididymal end largely unaffected. This action is not due entirely to antagonism of calcium influx. Verapamil unexpectedly potentiated the responses of the prostatic portion, and antagonized those of the epididymal end. The use of nifedipine may, therefore, allow investigations of adrenergic mechanisms on this tissue to be studied without the complications of non-adrenergic transmission.     

Post-natal development of functional neurotransmission in rat vas deferens.

Responses of the rat vas deferens to drugs and to field stimulation were examined in sexually immature rats. The vasa from immature rats often exhibited spontaneous contractions and displayed greater sensitivity to the contractile effects of alpha-adrenoceptor agonists. The responses of the vasa from immature rats to single pulse field stimulation lacked the adrenergic component of the response although the non-adrenergic component was present. The responses were antagonized by alpha 2-adrenoceptor agonists. In the presence of cocaine, an adrenergic component of the response did appear. During trains of pulses the pre- and postjunctional effects of adrenergic transmission which are found in adult rats were absent in vasa from immature rats. Electron microscopic studies showed no qualitative differences in adrenergic innervation in vasa from immature and adult rats. It is concluded that a state of 'pre-innervation supersensitivity' associated with a lack of functional adrenergic transmission exists in the vas deferens of immature rats. The supersensitivity disappears and functional transmission develops during the period in which testosterone secretion increases in the rat. The reason for the lack of functional transmission at a time when the innervation appears to be morphologically mature is not clear but may be due to the noradrenaline release mechanism not being fully operative.     

Postsynaptic potentiation of neurotransmission by neurokinin A in rat vas deferens.

Effects of neurokinin A (NKA) on sympathetic neurotransmission were studied in rat vas deferens. Although neither prazosin, an alpha 1-adrenoceptor blocker, nor alpha, beta-methylene adenosine triphosphate, a P2-purinoceptor blocker, inhibited the NKA-induced contractions in the epididymal site, high concentration of NKA-induced contractions in the prostatic site were slightly decreased by either of the two blockers. Treatment with guanethidine, which prevents the release of sympathetic transmitters from presynaptic nerve endings, also had no effect on NKA-induced contractions in either site. To investigate the effects of NKA on the adrenergic and purinergic neurotransmission in more detail, we measured transmitter release by using [3H]norepinephrine or [14C]adenosine. Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by electrical stimulation in the epididymal site, which may be originated from smooth muscle. In the prostatic site, contractions induced by electrical stimulation were enhanced in spite of no increase in 3H or 14C efflux. These results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site, and 3) NKA modulates the neurotransmissions.     

Inhibition by sulfur-containing amino acids and GABA of sympathetic neurotransmission in guinea-pig vas deferens

Electrical stimulation produced a contraction in the isolated guinea-pig vas deferens. This response was blocked by tetrodotoxin, guanethidine and bretylium but not by atropine. The magnitude of the contractile response to electrical stimulation depended on the concentration of the external calcium. Sulfur-containing amino acids and GABA inhibited the electrically induced contraction but not that caused by noradrenaline and ATP. The order of potency for inhibition of the contraction at a concentration of 10(-4) M being GABA greater than or equal to cysteine greater than methionine greater than cysteic acid greater than taurine. The contractile response to electrical stimulation was also inhibited by EGTA, this inhibition being similar to that by cysteic acid and taurine but weaker than that by methionine, cysteine and GABA at a concentration of 10(-4) M. The inhibitory action of sulfur-containing amino acids and GABA was abolished by increasing the calcium concentration in the medium. The results suggest that sulfur-containing amino acids and GABA reduce transmitter release from the sympathetic nerve terminals by inhibiting calcium availability for the transmitter secretion process.     

The mechanism of action of AMP-induced inhibition of sympathetic neurotransmission in the isolated vas deferens of the rat and guinea-pig.

1. The proposal that adenosine 5'-monophosphate (AMP) can be used as a selective antagonist of ATP at P2-purinoceptors on smooth muscle was investigated by examining the electrical and mechanical responses of guinea-pig and rat vasa deferentia to stimulation of sympathetic nerves and to exposure to exogenous agonists. 2. The magnitude of the contractile response of the rat vas deferens to field stimulation of the sympathetic nerves was reduced by addition of AMP. This effect was rapid in onset and readily reversed by washout. 3. The action of AMP on these contractile responses was reversed by the subsequent addition of the specific P1-purinoceptor antagonist 8-phenyltheophylline (8-PT). 8-PT on its own had no significant effect on contractile responses to nerve stimulation. 4. The magnitude of excitatory junction potentials (e.j.ps) in the guinea-pig vas deferens evoked by a train of stimuli at 0.5 Hz was reduced in a dose-dependent manner by introduction of AMP (10(-6)-10(-3)M). The inhibitory effect of 10(-5) M AMP on e.j.p. magnitude was completely and rapidly reversed by introduction of 10(-5)M 8-PT. The effect of 10(-4)M AMP was partially reversed by 10(-5) 8-PT. 5. The contractile responses of the guinea-pig vas deferens to exogenously applied adenosine 5'-triphosphate (ATP) were not reduced by AMP, even at a concentration of 2.5 X 10(-4)M. Similarly in the rat vas deferens, contractile responses to exogenously applied alpha, beta-methylene ATP (a more potent P2-purinoceptor agonist) were reduced by only 27.2%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Formation of dopamine and noradrenaline in rat vas deferens: comparison with guinea-pig vas deferens.

1 The formation of [14C]-3,4-dihydroxyphenylalanine (DOPA) from [14C]-tyrosine, in the presence of the amino acid decarboxylase inhibitor, brocresine (3-hydroxy-4-bromobenzyloxyamine dihydrogen phosphate), was greatly enhanced in rat vasa deferentia depolarized by a KCl-enriched Krebs-Henseleit solution (52 mM KCl) compared with tissues maintained in unmodified Krebs-Henseleit solution. 2 When the conversion of tyrosine was allowed to proceed as far as catecholamine (brocresine absent) no significant difference was observed between the accumulation of [14C]-catecholamines (CA) in depolarized rat vasa deferentia and the accumulation in control (non-depolarized) tissues. 3 Endogenous CA levels in the depolarized rat vasa deferentia fell to 67% of the controls after a 1 h incubation period and to 53% at the end of 2 hours. 4 Chromatographic separation on Amberlite CG-120 columns of the newly synthesized CA and catechol metabolites from the rat vas deferens revealed that a very high proportion was present as dopamine. The percentage distribution after 1 h incubation in control Krebs-Henseleit was: noradrenaline (NA): 30.6 +/- 5.2; dopamine 56.9 +/- 5.9; acid metabolites: 12.8 +/- 1.1; and in KCl-rich Krebs-Henseleit, NA: 32; dopamine: 44.7 and acid metabolites 23.3. In contrast to the newly synthesized (14C-labelled) CA, endogenous dopamine comprises only 10% of the endogenous CA stores in rat vas deferens. 5 The distribution of newly synthesized NA and dopamine in rat vas deferens is strikingly different from that of guinea-pig vas deferens where more than 80% of newly formed amine is present as NA. In the latter tissue depolarization with K+ causes a striking increase in CA biosynthesis.     

Elucidation with the protease alpha-chymotrypsin of the inhibitory modulating action of endogenous neuropeptide Y over sympathetic neurotransmission in rat vas deferens

The physiological role of endogenous neuropeptide Y (NPY) in sympathetic neurotransmission was examined in rat and guinea pig vas deferens (VD), using alpha-chymotrypsin (alpha-CT). NPY-like immunoreactivity was detected in the longitudinal muscle layer of VD densely in rats but sparsely in guinea pigs, and it disappeared following surgical denervation. Under blockade of the prejunctional alpha(2)-adrenergic autoinhibition, alpha-CT potentiated the phasic contraction in rat, but not guinea pig, VD induced by trains of transmural nerve stimulation (TNS) in a frequency-dependent manner, which was reproducible during repeated applications and not affected by pretreatment with capsaicin. In contrast, alpha-CT did not potentiate the twitch response or contractions induced respectively by a single pulse TNS or by direct electrical stimulation to the smooth muscle. Exogenously applied NPY suppressed the twitch response, which was cancelled by alpha-CT, and excitatory junction potentials, although it affected neither spontaneous junction potentials nor the direct electrical stimulation-induced contraction. These observations provided further evidence to support that NPY is released endogenously by TNS at high frequency, acting prejunctionally to suppress sympathetic neurotransmission. Thus, the protease alpha-CT proved itself to be a useful tool to reveal a functional role of endogenously released peptides.     

Pharmacological comparison between the actions of methamphetamine and 1-aminoindan stereoisomers on sympathetic nervous function in rat vas deferens

The selective monoamine oxidase-B inhibitor selegiline (deprenyl) causes sympathomimetic effects and is metabolised to R(-)-methamphetamine and R(-)-amphetamine. The new monoamine oxidase-B inhibitor rasagiline is devoid of sympathomimetic effects and is metabolised to R(+)-1-aminoindan. Sympathomimetic effects of methamphetamine and 1-aminoindan enantiomers were compared in the rat vas deferens. R(-)-methamphetamine and S(+)-methamphetamine caused initial potentiation and subsequent inhibition of the field stimulation-induced twitch response of isolated rat vas deferens (0.1 Hz). EC(50) values for inhibition of twitch in prazosin-treated vas deferens were 0.36+/-0.13 and 1.64+/-0.10 microM (mean+/-S.E.M.) for S(+)- and R(-)-methamphetamine, respectively. There was no difference between S(+)-methamphetamine and R(-)-methamphetamine in potentiation of postsynaptic contractile response to noradrenaline. R(+)- and S(-)-1-aminoindan increased twitch response only at concentrations above 30 microM. R(-)-methamphetamine has similar potency to S(+)-methamphetamine in potentiation of noradrenaline-mediated responses and can therefore play a role in the sympathomimetic effects of selegiline.     

Unique effect of tetrapentylammonium ions on sympathetic transmission in rat vas deferens

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Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease.     

Nitric oxide as neuromodulator of sympathetic transmission in rat vas deferens

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