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[Influence of denervation on metabolism of phospholipid in the rat vas deferens].

Influence of denervation on phospholipid metabolism in the vas deferens and effect of phospholipase C treatment on sensitivity of the vas deferens for noradrenaline were studied. The incorporation of 32P-orthophosphate into phosphatidylethanolamine and phosphatidylcholine was markedly increased by denervation. Incorporation of 32P-orthophosphate into proteolipid was accelerated more than that of 3H-leucine. Sensitivity of the denervated vas deferens for noradrenaline was strongly reduced by phospholipase C treatment. These data suggest that the supersensitivity of the denervated vas deferens for noradrenaline was mainly due to the increase in phospholipids.

Animals↗

Mu-receptors in the C57BL mouse vas deferens.

The C57 mouse vas deferens preparation has been shown to be insensitive to mu-opioids. The present study indicates that this tissue possesses mu, d and k-receptors with similar affinities to those found in other isolated tissue preparations, but has a small receptor reserve. Thus partial agonists such as morphine are detected as antagonists.

Animals↗

Neurotransmitters adenosine triphosphate and noradrenaline induce nitric oxide release in rat vas deferens.

1. In rat vas deferens, electrical field stimulation (EFS) evoked a muscular biphasic tetrodotoxin (TTX)-sensitive contractile response. 2. The amplitude of this response increased with the frequency of stimulation. 3. After each stimulation, nitric oxide (NO) release was assayed and found to be released in a frequency-dependent manner. 4. NO release also occurred after treatment with exogenous neurotransmitters, adenosine 5'-triphosphate (ATP) and noradrenaline (NA). 5. Prazosin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), respective antagonists of alpha1-adrenoceptors and P2x purinoceptors, inhibited NO release induced by NA and ATP. Both prazosin and PPADS inhibited NO release by EFS. 6. TTX failed to modify the NO release induced by exogenous neurotransmitters but abolished the release of NO and contractile response by EFS. 7. EFS and released noradrenaline and ATP induce the release of NO through postjunctional alpha1 -adrenoceptors and P2x-purinoceptors, respectively.

Adenosine Triphosphate↗

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

In the rat vas deferens, DMPP is a substrate of uptake1 (Km = 11.5 mumol/l). 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) mumol/l DMPP induced a hexamethonium-sensitive release of 3H-noradrenaline of short duration. Hence, in the presence of extracellular calcium, 100 mumol/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 mumol/l.

Animals↗

Calcium reverses the inhibitory action of morphine on neuroeffector transmission in the mouse vas deferens.

In the mouse vas deferens, the amplitude of excitatory junction potentials (e.j.p.s.) recorded intracellularly from smooth muscle cells was found to be proportional to stimulus intensity. Normorphine (0.4-2-10 microM) reduced the amplitude of these postsynaptic transients and shifted the stimulus-response curve to the right; i.e. in its presence, higher stimulus intensities were required to elicit an e.j.p. of a similar size to one generated in its absence. Naloxone (0.4 microM) reversed the inhibitory effect of normophine (2 microM). Membrane potentials were unaffected by the concentrations of normorphine employed in solutions of varying ionic compositions. Manoeuvres designed to increase intracellular free calcium, that is increasing the extracellular Ca+ ion concentration (from 2.5 to 5 or 10 mM), removing Mg2+ ions from a medium containing 5 mM Ca2+ or applying 4-aminopyridine (100 microM), enhanced the e.j.p. amplitude and reversed the inhibitory effect of normorphine. Lowering the concentration of Ca2+ ions (from 2.5 to 1 mM) or increasing the concentration of Mg2+ ions (from 1.2 to 4.8 mM) in the bathing solution reduced the amplitude of e.j.p.s. Short trains of impulses (3Hz) facilitated the amplitude of successive e.j.p.s., probably by elevating the intracellular Ca2+ ion concentration. The inhibitory effect of normorphine upon these transients was inversely proportional to the length of the train. It is concluded that the reversal of the effect of normorphine by calcium does not occur at the level of the opiate receptor, and that the opiate depresses the stimulated release of the excitatory transmitter by a reduction in the supply of Ca2+ ions to the stimulus-release coupling mechanism in the sympathetic nerve terminals.

Aminopyridines↗

Effects of streptozotocin-induced diabetes and insulin on calcium responsiveness of the rat vas deferens.

In the present study, effects of streptozotocin-induced diabetes and insulin treatment on the reactivity of rat vas deferens to KCl and calmidazolium, a calmodulin antagonist, were evaluated and calmodulin levels in vas deferens tissue from diabetic and insulin-treated rats were determined. Diabetes was induced in rats by a single injection of streptozotocin. Five weeks after the induction of diabetes, one group of diabetic rats was injected with insulin for 3 weeks. After 8 weeks, vas deferens tissues on one side of diabetic and insulin-treated diabetic rats and their controls were mounted in organ bath to measure isometric tension, while the tissues on the other side of rats were homogenized to determine calmodulin levels by radioimmunoassay. Concentration-response curves to KCl were obtained in vas deferens tissues in the absence and presence of calmidazolium. The effects of KCl and calmidazolium on vas deferens isolated from 8-weeks diabetic rats were decreased. Calmodulin levels were also found to be decreased in vas deferens from diabetic rats. Decreased calmodulin levels in diabetic rat vas deferens were not corrected by insulin treatment. Only a partial correction following insulin treatment was observed in contractile effect of KCl on diabetic rat vas deferens, whereas insulin treatment increases the affinity of calmodulin in this muscle. Experimental diabetes causes an impairment in calcium/calmodulin-dependent contractile process of vas deferens, which is correctable partially following insulin therapy. The changes in the function of rat vas deferens due to streptozotocin diabetes seem to be related to impaired sexual functions in human diabetes.

Adrenergic alpha-Agonists↗

Sympathetic efferent pathways projecting to the vas deferens.

The abdominal and pelvic sympathetic nervous system controlling the vas deferens has elaborate mechanisms to preserve its function against various injuries. The main sympathetic signals to the vas deferens proceed the common pathway in mammalians, which consists of the lumbar splanchnic nerve, caudal mesenteric plexus, hypogastric nerve, pelvic plexus and its branches. On the way of this common pathway, some signals cross to the other side of the body at the level of the caudal mesenteric plexus and/or the pelvic plexus. The preganglionic axons passing through the hypogastric nerve very likely provide a bilateral innervation to postganglionic neurons in the pelvic plexuses, which also exhibit crossing to the bilateral vasa deferentia. The sympathetic nerves originating from the thoracic spinal cord are of minor importance in contraction of the vas deferens but possibly influence it by the hormonal system consisting of the major splanchnic nerve and the adrenal medulla. When the common pathway is interrupted, various compensatory mechanisms are generated: enhancement of the remaining sympathetic pathways or reorganization of synaptic connection in the pelvic plexus. Surgical reconstruction of the transected hypogastric nerve is possible and cross-innervation mechanism via the hypogastric nerve can also be preserved. Elevation of intraluminal pressure at the cauda epididymis/proximal vas deferens induced by nerve impulse pushes the spermatozoa out to the ampulla and distention of the wall of the ampulla triggers its contraction to emit the content into the urethra. After seminal emission, a portion of the seminal fluid remaining in the vas deferens moves in a retrograde direction to the cauda epididymis for the next emission. It remains to be seen whether similar mechanisms in animals are at work in humans.

Adrenal Medulla↗

The effects of adenosine on receptor sensitivity in the rat vas deferens.

In the guinea-pig isolated vas deferens adenosine augments the contractile response to noradrenaline (NA). Adenosine also augments the contractile response to NA and phenylephrine in the prostatic portion of the transversely bisected rat vas deferens. However, adenosine appeared to neither augment nor diminish the responses to carbachol, 5HT or high K+. Repetitive exposure of the vas to various agonists induced a desensitisation specific to the particular agonist used. The rate of return of responsiveness (the rate of resensitization) was investigated and, in particular, the effect of adenosine on that rate. In the rat vas deferens the rate of resensitization of responses to NA was retarded by adenosine and this effect was abolished by 8-phenyltheophylline and by yohimbine, but not by atropine or propranolol. Neither 8-phenyltheophylline, yohimbine, propranolol nor atropine by themselves affected the rate of resensitization of the rat alpha-adrenoceptor. Adenosine had no effect on the rate of resensitization of responses to phenylephrine, 5HT, carbachol or high K+. It is considered that the potentiation of catecholamine responses by adenosine involves solely alpha 1-receptors but that the retardation of resensitization may involve alpha 2-receptors which do not contribute directly to contraction.

Adenosine↗

Analysis of spermatozoa from the proximal vas deferens of fertile men.

Fluids from the left and right proximal vas deferens were collected from 105 normal fertile men by cannulating the vas deferens during vasectomy, and sperm parameters analysed. Sperm motility (73.1 +/- 13.3%), normal sperm morphology (75.2 +/- 11.1%), sperm viability (72.7 +/- 18.8%) and the hypo-osmotic swelling test (73.3 +/- 19.2%) were in the normal range, compared with that of ejaculated spermatozoa. However, sperm concentration in the proximal vas deferens (6274.6 +/- 5103.8 x 10(6) ml-1 was higher than that in semen. Sperm concentration in the right vas deferens was significantly higher (P < 0.05) than that in the left and the percentage of spermatozoa showing abnormal cervical mucus penetration was significantly higher (47%) for the left than for the right (18%). There were no anti-sperm antibodies on the surface of spermatozoa from the vas deferens as determined by the sperm cervical mucus contact test and immunobead test. These parameters of spermatozoa from the proximal vas may reflect those of spermatozoa from the human cauda epididymis.

Adult↗

Clinical, andrological and genetic characteristics of patients with congenital bilateral absence of vas deferens (CBAVD).

Congenital bilateral absence of the vas deferens (CBAVD) is a form of infertility with an autosomal recessive genetic background in otherwise healthy males. In this study, we examined the clinical and cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations in sixty patients with bilateral absence of vas deferens that applied to andrology clinic due to male factor infertility. Urogenital anomalies of vas deferens, seminal vesicle and epididymis were detected in our patient group. CFTR gene mutations, which are known to be frequent among cystic fibrosis patients, could not be detected in our patient group with that high frequency. Delta F508 mutations were detected in only 6% of patients. IVS8 polyT alleles were positive in 68% of patients. No 1677delTA mutations and M470V variants were detected in our patient group. However, sperm retrieval is almost always possible from CBAVD patients; secondary pathologies may also result defective spermatogenesis.

Abnormalities, Multiple↗

Ionic currents in single smooth muscle cells of the human vas deferens.

PURPOSE: Smooth muscle cells of the vas deferens have an important role in carrying sperms to the exterior but little is known of their electrophysiological properties. We characterized the voltage-gated ion channel currents in single smooth muscle cells of the human vas deferens (HVSMCs). MATERIALS AND METHODS: We observed contractile responses of 8 circular smooth muscle strips of the human vas deferens to a high concentration (10 mM) of tetraethylammonium. HVSMCs were isolated using proteolytic enzymes (collagenase and papain), and were used for an electro-physiological study using whole cell and inside-out patch clamp configurations. RESULTS: The application of 10 mM tetraethylammonium induced rhythmic contractions of the strips. When HVSMCs were dialyzed with a KCl solution, step depolarizations of membrane potential evoked oscillatory outward K currents that were not inactivated. The large conductance Ca activated K (BKCa) and delayed rectifier components of the outward current were identified. The BKCa channel showed a large single channel conductance (162.7 +/- 13.2 pS with 5 mM K in the patch pipette). Two types of Ca currents were identified in the whole cell configuration. With a cell held at -50 mV an L-type Ca current was present during a depolarizing step pulse. From a holding potential of -90mV L-type and T-type Ca currents were elicited by depolarizing step pulses. CONCLUSIONS: HVSMCs have 2 (L and T) types of Ca channels and 2 types of K (BKCa and delayed rectifier) channels. Voltage dependent changes of these ion channels and their interactions may be important in regulating vas contractility.

Adult↗

Morphological changes of spermatozoa in proximal vas deferens after vasectomy.

AIM: To investigate the morphological changes of spermatozoa in the proximal vas deferens after vasectomy. METHODS: Proximal vas deferens fluids were collected from 79 fertile men (group A) and 64 vasectomized men (group B) during the operations of vasectomy or vasovasostomy. Sperm morphology in the proximal vas deferens was analyzed after staining with the modified Papanicolaou method. RESULTS: The percentage of spermatozoa with a normal oval head from group B (50. 7% +/- 21.7%) was significantly lower than that of group A (75.2% +/- 11.1%). The data in group A was similar to those of normal semen and therefore represents the physiological condition of the proximal vas deferens sperm of fertile men. There were no significant differences in the percentages of normal oval heads in group B with the time since vasectomy. CONCLUSION: After vasectomy, the spermatozoa in the proximal vas deferens and epididymis were continuously degenerating and being replenished by spermatozoa coming from testis. The obvious morphological degeneration occurred in the sperm tail and spermatozoa with a small oval head and amorphous heads were increased.

Adult↗

Adenosine stimulates anion secretion across cultured and native adult human vas deferens epithelia.

Experiments were conducted to determine the responsiveness of human vas deferens epithelial cell monolayers to adenosine and related agonists. Human abdominal vas deferens epithelial cells have been isolated from adult tissues and grown to confluence on permeable supports. All cells exhibit intense ZO-1 and cytokeratin immunoreactivity. Cultured cell monolayers exhibit high electrical resistance with a lumen-negative potential difference and short circuit current (I(sc)) indicative of anion secretion and/or cation absorption. A portion of the basal I(sc) is inhibited by amiloride. Amiloride-sensitive I(sc) is enhanced by exposure to glucocorticoids and is Na(+) dependent, indicating the presence of epithelial sodium channel-mediated Na(+) absorption. Epithelial anion secretion and intracellular generation of cAMP are acutely stimulated by adenosine and the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA), with these effects being fully blocked by 8-phenyltheophylline. Adenosine receptors are localized to the apical membrane of the epithelial cells, as basolateral adenosine is without effect. Freshly excised human vas deferens recapitulate observations made on cultured epithelia when evaluated with the self-referencing vibrating probe: amiloride inhibition of basal ion transport, stimulation by adenosine, and inhibition by 8-phenyltheophyline. These results demonstrate that adult human vas deferens epithelium actively transports ions to generate the luminal environment of the deferent duct. Thus, vas deferens epithelium likely plays an active role in male fertility, and interventions that modulate epithelial function might be exploited to treat male-factor infertility or in contraception.

Adenosine↗

Specific H+/K(+)-ATPase inhibitors decreased contractile responses of isolated rat vas deferens.

The effect of H(+)/K(+)-ATPase inhibitors on rat vas deferens contractility was investigated in vitro. Omeprazole (100-300microM), lansoprazole (100-300microM) and SCH 28080 (10-100microM) (2-methyl-8-(phenylmethoxy)-imidazo[1,2-a]pyridine-3-acetonitrile) decreased contractile responses of vas deferens to electrical field stimulation, high K(+) (80mM) and phenylephrine in a reversible, reproducible and concentration-dependent manner. The inhibitory potency of lansoprazole on vas deferens contractility was increased in relatively acidic solution (pH 6.9), suggesting that the site of action may be related to H(+)/K(+)-ATPase. However, lansoprazole-induced inhibition on contractility was unaltered in K(+) free solution, indicating that the mechanism of action is independent from H(+)/K(+)-ATPase. Reversible nature of omeprazole and lansoprazole-induced inhibition on contractility also suggests that the effects are not due to inhibition of H(+)/K(+)-ATPase, since both compounds are irreversible inhibitors of the enzyme. Presence of ouabain (5microM) did not decrease lansoprazole-induced inhibition on contractility but potentiated the inhibitory effect of lansoprazole, suggesting that lansoprazole-induced inhibition is not mediated by the inhibition of Na(+)/K(+)-ATPase. Calcium-induced contractions in high K(+)-Ca(2+) free medium were completely antagonized by lansoprazole, implying that lansoprazole inhibits Ca(2+) entry through voltage-gated channels. In conclusion, three H(+)/K(+)-ATPase inhibitors decreased contractile responses of rat vas deferens to various stimulants in vitro. They may act on a common mechanism, which plays a crucial role in regulating rat vas deferens contractility and this mechanism is probably involved in the regulation of intracellular Ca(2+).

2-Pyridinylmethylsulfinylbenzimidazoles↗

A study of the mechanism of action of aminoglycoside antibiotics on the guinea pig vas deferens.

Aminoglycoside antibiotics inhibit contractility of the isolated guinea pig vas deferens in a dose-related manner. However, total inhibition of the contractility cannot be attained, a phenomenon most probably attributed to the partial inhibition of the function of Ca channels by the antibiotics. The inhibitory potency of aminoglycoside antibiotics was found to be: sisomicin greater than gentamicin greater than netilmicin greater than streptomycin greater than dactimicin greater than amikacin greater than kanamycin greater than kanendomycin greater than dibekacin greater than tobramycin. Ca2+ antagonize the action of aminoglycoside antibiotics on the vas deferens competitively. This observation indicates that the untoward effect of aminoglycoside antibiotics on contractility of the vas deferens can be attributed to their ability to interfere with Ca2+ entry through cell membranes of the tissue, a prerequisite for subsequent contraction. Above a specific threshold (7.5 mM) Ca2+ have a prophylactic effect on vas deferens and prevent the inhibitory action of ICmax doses of the antibiotics. Thus, Ca could be used as a prophylactic medium or as an antidote in restoring contractility of the vas deferens if it is inhibited by aminoglycoside antibiotics.

Animals↗

Investigation of the subtypes of alpha 1-adrenoceptor mediating contractions of rat aorta, vas deferens and spleen.

1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) or phenylephrine in rat vas deferens, spleen and aorta, and mediating contractions to endogenous NA in rat vas deferens have been examined. 2. In rat vas deferens, the competitive antagonists prazosin, WB 4101, benoxathian and 5-methyl-urapidil inhibited contractions to NA with pA2 values of 9.26, 9.54, 9.02 and 8.43, respectively. The irreversible antagonist chloroethylclonidine (CEC) (100 microM) failed to affect contractions to NA. 3. In rat vas deferens in the presence of nifedipine (10 microM), contractions to NA were significantly attenuated and under these conditions, CEC (100 microM) significantly reduced the maximum response to NA. 4. In rat spleen, the competitive antagonists prazosin, WB 4101 and benoxathian inhibited contractions to phenylephrine with pA2 values of 9.56, 8.85 and 7.60, respectively, and 5-methyl-urapidil had a KB of 6.62. CEC (100 microM) significantly reduced the maximum contraction to phenylephrine. 5. In rat aorta, the competitive antagonists, prazosin, WB 4101, benoxathian and 5-methyl-urapidil inhibited contractions to NA with pA2 values of 9.45, 9.21, 8.55 and 8.12, respectively. CEC (100 microM) produced an approximately parallel shift in the potency of NA, without significantly reducing the maximum response. 6. In epididymal portions of rat vas deferens in the presence of nifedipine (10 microM), the isometric contraction to a single electrical pulse was significantly reduced by CEC (100 microM), and by the competitive antagonists prazosin, WB 4101, benoxathian and 5-methyl-urapidil at concentrations of 1 nM. 7. In prostatic portions of rat vas deferens, the alpha l-adrenoceptor agonist, amidephrine, produced concentration-dependent increases in the isometric contraction to a single electrical stimulus and the maximum increase in the evoked response produced by amidephrine was unaffected by CEC (100 microM).8. Contractions of rat vas deferens produced by NA (and amidephrine) are mediated predominantly by alpha lA-adrenoceptors as shown by the high potency of alpha lA-adrenoceptor selective antagonists and the lack of effect of CEC. A small CEC-sensitive response, particularly in epididymal portions, was revealed in the presence of nifedipine. Contractions of rat spleen are mediated by alpha lB-adrenoceptors since alpha 1A selective antagonists showed low potency and CEC significantly reduced the maximum contraction to phenylephrine. Contractions of rat aorta to NA are mediated by non-alpha lA, non-alpha lB-adrenoceptors, due to the high potency of the aMA-selective antagonists and sensitivity to CEC.9. The noradrenergic contraction of epididymal portions of rat vas deferens in the presence of nifedipine is CEC-sensitive, but the alpha 1 A-selective antagonists showed high potency, suggesting that this response is mediated by non-alpha lA, non-alpha 1B-adrenoceptors.10. In conclusion, at least three subtypes of functional alpha 1-adrenoceptors have been demonstrated in these studies.

Adrenergic alpha-Agonists↗

Relationship between alpha-adrenoceptor occupancy and contractile response in rat vas deferens. Experimental and theoretical analysis.

The rat vas deferens has been considered to be the tissue of choice to study alpha-adrenergic drugs. However, some of these agonists have elicited complex responses in this organ. Therefore, detailed characterization of alpha-adrenoceptor-mediated responses of the rat vas deferens was the aim of this work. Experiments were designed to study the contractile response of this tissue to phenylethanolamine (noradrenaline) and to two imidazolines (oxymetazoline and naphazoline). These responses were related to receptor occupancy and to other parameters of drug action, i.e. dissociation constants, relative efficacies, ED50 and maximal responses. A theoretical model was used to check the experimental data. There was a non-linear relationship between response and receptor occupancy with all three agonists. The dissociation constants for noradrenaline, oxymetazoline and naphazoline were 11.06, 0.15 and 0.10 microM, respectively. The rat vas deferens had 75-80% spare receptors for noradrenaline. Oxymetazoline and naphazoline were shown to be partial agonists with low relative efficacies as compared to noradrenaline (0.0063 and 0.0056 respectively). The dose-response curves generated by the model for partial agonists were similar to the curves obtained experimentally in vitro.

Animals↗

Congenital ectopic vas deferens inserting into the bladder with ipsilateral renal agenesis.

Vas deferens ectopia is a rare congenital anomaly which is frequently associated with anorectal abnormalities. There have been 20 cases up to date with an ectopic vas deferens inserting into the ureter. Out of these 6 had a bilateral insertion and another 4 cases with an ectopic vas deferens inserting directly into the bladder, out of which 1 had a bilateral insertion. There is an embryological hypothesis which may explain this rare condition that may result from a possible underlying defect of the proximal vas precursor segment of the Wolffian duct. Herein, we present a case of an ectopic vas deferens terminating in the urinary bladder and accompanied by ipsilateral renal agenesis. This is the second case report in the world literature.

Abnormalities, Multiple↗