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Effects of the high K+/Na+ deficient solution on mechanical response and wet weight of tissue in vas deferens and seminal vesicle in guinea-pig.

In the present experiments, we investigated contractions of guinea-pig vas deferens or seminal vesicle in various kinds of high K+ solution. The vas deferens showed a phasic contraction followed by a tonic one in hyperosmotic 65 mM KCl (hyper-65K+), isosmotic 60 mM or 120 mM KCl solution. However, isosmotic 154 mM KCl (iso-154K+) solution induced a large phasic contraction followed by a gradual relaxation. Applications of the high K+ solutions to the preparation of seminal vesicle showed almost similar results in tension to those of the vas deferens. In the vas deferens or seminal vesicle, an application of hyper-65K+ solution significantly decreased the relative value for the wet weight of the tissue at 120 min, but that of iso-154K+ solution did not affect the wet weight of both the muscles. In the vas deferens, an hyperosmotic addition of sucrose at a concentration of 25 to 100 mM slightly prevented the tension decreased by the iso-154K+ solution and slightly decreased the relative wet weight. In the seminal vesicle, increasing sucrose concentration significantly increased the tension, but decreased the relative wet weight. In both the muscles of vas deferens and seminal vesicle, an addition of pyrvate or oxalacetate (5.5 mM) to the iso-154K+ solution without glucose maintained the muscle tension at a maximal level in the iso-154K+ solution with glucose for 120 min. Further, the tension decrease in both the muscles induced by iso-154K+ solution was also prevented by hyperosmotic application of NaCl. From these results, it is suggested that the tension decrease by high K+, Na+-deficient solution in the vas deferens is mainly caused by an inhibition of glucose utilization by Na+-deficiency in the medium, however, the seminal vesicle is probably due to the cell swelling and partly the inhibition of glucose utilization by it.

Animals↗

Assessment of selectivity of muscarinic antagonists for M1 and M2 receptors in rabbit isolated vas deferens.

Neurogenic contractions of the rabbit isolated vas deferens were inhibited by McN-A-343 but potentiated by carbachol. The actions of McN-A-343 and carbachol on the twitch contractions were antagonized to different degrees by antimuscarinic drugs: the affinity (pA2) of atropine and himbacine against McN-A-343 and carbachol was similar. However, pirenzepine and telenzepine displayed preferential antagonism of McN-A-343 responses, whereas the converse was true for methoctramine and AF-DX 116. The pA2 values of 6 antagonists against carbachol responses in rabbit vas deferens closely agree with those obtained in rat left atrium. In unstimulated organs carbachol and McN-A-343 had no effect on the resting tension. Contractions elicited by ATP, noradrenaline and KCl were potentiated by carbachol but were unaffected by McN-A-343. The data suggest the presence of a presynaptic M1 receptor mediating inhibition and a postsynaptic, cardiac-like M2 receptor enhancing neurogenic contractions in rabbit vas deferens.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Pharmacological effects of meptazinol and its enantiomers on guinea-pig ileum and mouse vas deferens.

Electrically induced twitch responses of mouse vas deferens and guinea-pig ileum were inhibited by morphine, normorphine and the peptide opioid agonist RX783006; naloxone blocked the effects of all three opioid agonists yielding Ke values which were not significantly different and which were within the range (1-4 nM) expected for mu-type receptors. At concentrations between 0.1 and 10 microM (+)-meptazinol inhibited the twitch response of the ileum while (-)-meptazinol produced potentiation. Naloxone (20 nM) completely blocked the effect of (+)-meptazinol and further increased the potentiation produced by (-)-meptazinol. In the mouse vas deferens preparation neither isomer affected the electrically induced twitch response at concentrations below 5 microM and higher concentrations (10-300 microM) produced potentiation. Naloxone (20 nM) did not modify this effect. It is concluded that both isomers are opioid agonists on the mu-receptors in guinea-pig ileum but not in mouse vas deferens and that a cholinergic component, which may contribute to the action of meptazinol in-vivo, is present to a smaller extent in the (+)-isomer.

Animals↗

Characterization of somatostatin receptors in guinea-pig isolated ileum, vas deferens and right atrium.

1. Somatostatin14 (SS14) inhibits neurogenically mediated contractile responses in guinea-pig ileum and vas deferens and exerts a direct negative inotropic action in guinea-pig spontaneously beating right atrium. In this study, the receptors mediating these inhibitory effects have been characterized by comparing the potencies of several cyclic somatostatin analogues. 2. In the guinea-pig ileum, SS14, somatostatin28 (SS28), somatostatin25 (SS25) and several smaller cyclic somatostatin analogues including octreotide, angiopeptin and CGP 23996, inhibited neurogenically mediated contractile responses, each being of similar potency. 3. In contrast, in the guinea-pig vas deferens and right atrium, SS28 was about 30 times more potent than SS14. However, although angiopeptin was nearly as potent as SS14 as an agonist in the vas deferens, in guinea-pig atrium angiopeptin had low intrinsic activity and antagonized the negative inotropic action of both SS14 and SS28 (pKB values of 7.4 and 7.2, respectively). CGP 23996 was 2-7 times weaker than SS14 in guinea-pig vas deferens and atria. 4. Phosphoramidon (1 microM) and amastatin (10 microM) did not influence the potency of SS14 or SS28 in either the guinea-pig ileum or right atrium. In the guinea-pig vas deferens, phosphoramidon and amastatin did not affect the potency of SS28, but enhanced the potency of SS14 about 5 fold. Despite the presence of phosphoramidon and amastatin, SS28 was still more potent than SS14 in the vas deferens. 5. The putative somatostatin receptor blocking drug, cyclo(7-aminoheptanoyl Phe-D-Trp-Lys-Thr[Brl]) (CPP; 1 microM), did not antagonize the effects of either SS14 or SS28 in ileum, vas deferens or atrial preparations. 6. Somatostatin14 did not modify the contractile action of carbachol or alpha,beta-methylene ATP in the ileum and vas deferens respectively, suggesting that the site of the inhibitory effects on neurogenically mediated contractile responses in both preparations was pre-junctional. Consistent with this conclusion was the observation that the inhibitory effect of SS14 was markedly and inversely related to the external Ca2+concentration. The inhibitory effect of SS14 in guinea-pig atrium was only partly dependent on the external Ca2+ concentration.7. The somatostatin receptors mediating the inhibitory effect of SS14 in the ileum and vas deferens can be distinguished by the differential relative potencies of SS14 and SS28. In the former, SS14 and SS28 have similar potency whilst in the latter SS28 is much more potent. In this respect, the somatostatin receptor mediating negative inotropy in the guinea-pig right atrium appears similar to that identified in the vas deferens.8. We suggest that the somatostatin receptor mediating inhibition of neurogenic contraction in the ileum is similar to the recently cloned SSTR2 receptor. In contrast, the somatostatin receptor mediating negative inotropy in the atrium and inhibition of neurotransmission in the vas deferens appears similar to the SSTR4 receptor which recognises SS28 with higher affinity than SS14.

Amino Acid Sequence↗

Effects of alpha-adrenoceptor agents on norepinephrine release from vas deferens of several species including man.

Unlike the situation with the vas deferens of rats, guinea-pigs, rabbits and dogs, neither phentolamine nor yohimbine enhanced electrically-evoked release of [3H]norepinephrine from the in vitro human vas deferens. However, clonidine produced, by a phentolamine-sensitive mechanism, a concentration-related inhibition of release in the human vas deferens. The results indicate that, even though presynaptic alpha-adrenoceptors exist, a negative feedback regulation of release by norepinephrine, which occurs in the vas deferens of the other species, may not be functionally important in the vas deferens of the human.

Adrenergic alpha-Agonists↗

Mechanisms underlying the differential sensitivity to alpha 1-adrenoceptor activation in the bisected rat vas deferens.

1. The factors underlying the different responsiveness of the prostatic and epididymal portions of rat vas deferens to alpha 1-adrenoceptor stimulation were investigated. 2. The alpha 1-adrenoceptors in membranes of both halves of rat vas deferens were labelled with [3H]-prazosin and the affinities of agonists and antagonists for these receptors were determined. In saturation studies, the Bmax and KD values for [3H]-prazosin in membranes of both portions were the same. 3. In competition studies, the inhibition curves for phentolamine were biphasic and consistent with the presence of both alpha 1a- and alpha 1b-adrenoceptor subtypes. The proportions of binding sites with high and low affinity for phentolamine in both halves of rat vas deferens were similar and in good agreement with the percentages of binding sites for WB-4101 and phentolamine previously reported in the whole rat vas deferens. 4. The phenylethylamines displaced [3H]-prazosin with a shallow inhibition curve. The data are compatible with the assumption of two affinity states for the binding sites. For the imidazoline compounds no such distinct affinity states could be demonstrated. 5. The affinity for, and the relative intrinsic efficacy on postsynaptic alpha 1-adrenoceptors of both portions of rat vas deferens were studied for noradrenaline, phenylephrine and methoxamine by irreversible inactivation of the alpha 1-adrenoceptors by phenoxybenzamine. The parameters for partial agonists were determined by comparing the responses to the partial agonist to those of a full agonist in the same tissue. Homogeneous estimates of the equilibrium dissociation constants (Ka) were obtained, indicating that these agonists bind to the receptors of both tissues in an identical manner. Further, estimation of the intrinsic efficacy of agonists relative to noradrenaline, indicated no differences between the two halves of rat vas deferens. 6. Ka values for agonist activation of the functional alpha 1-adrenoceptors were compared with K, values for agonist inhibition of specific [3H]-prazosin binding. The K. values were well correlated with the low affinity K, values for phenylethylamines in both portions of rat vas deferens, suggesting that the initial event in signal transduction by alpha 1,-adrenoceptors is the binding to the low affinity state of the receptor. 7. There was a non-linear relationship between response and receptor occupancy in both halves of rat vas deferens but the occupancy-response coupling was more efficient in the epididymal than in the prostatic portion. This fact may account for the differences observed in the functional responses.

Adrenergic alpha-Agonists↗

Fine structural studies of the rat vas deferens.

A fine structural study of the normal rat vas deferens was undertaken utilizing perfusion fixation. Morphological features not previously appreciated were revealed using this technique of fixation, and included the following. The rat vas deferens exhibited a gross morphological and microscopic differentiation along its length: A proximal segment was characterized by a thin muscular wall, an epithelium of low height (comparable to that of the cauda epididymidis) and a distended lumen typically filled with an accumulation of sperm; a distal segment exhibited a thick muscular wall, a convoluted mucosa, and a pseudostratified columnar epithelium with long stereocilia extending into the lumen. The transition from the morphology typical of the proximal segment to that of the distal segment was gradual and progressive, marked by an increase in the mass of the muscular wall and in the height and ultrastructural complexity of the epithelium. Clear or "foamy" cells, characteristic of the cauda epididymidis, were observed in the initial centimeter of the vas deferens. Also, a cell type designated as "mitochondrion-rich" was observed in the distal vas segment. The structure of the small mitochondria in such cells, however, did not conform to the description of mitochondria in similar cells found in the human (Hoffer, '76). Intraepithelial macrophages containing residual accumulations which often resembled spermatozoan remnants in advanced stages of dissolution were present in all segments of the rat vas deferens, confirming in this species a spermiophagic role for such cells.

Animals↗

Calcium modulatory properties of 2,6-dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations.

1. In rat isolated vas deferens the new compound 2,6-dibutylbenzylamine (B25) evoked a series of repeating rhythmic contractions. Concentration-response curves constructed for this effect were bell-shaped, indicating a biphasic effect for this compound. By contrast, B25 depressed heart contractility without any visible positive inotropic or chronotropic activity. 2. Experiments with tetrodotoxin, reserpine, capsaicin, alpha-adrenoceptor blocking compounds and other agents permit us to exclude a release of neuromediators or a direct stimulation of post-synaptic receptors to account for the rhythmic effect of B25 in the rat vas deferens. 3. In the same tissue, the increase in 45Ca2+ uptake, the voltage-dependency as well as the dependence of the B25-induced rhythmic activity upon the external calcium concentration indicate a direct activation of voltage-sensitive calcium channels (VSCC). 4. Verapamil paradoxically stimulated the rhythmic effect of B25 in the rat vas deferens. La3+ was inactive while nifedipine was a weak inhibitor. By contrast Ni2+ and Mn2+ ions were good inhibitors (IC50 < 10(-4) M), suggesting that a possible opening of T-type VSCC underlies rhythmic effect of B25. 5. In radioligand binding studies competition experiments with [3H]-nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine-sensitive binding sites of heart and vas deferens smooth muscle. 6. B25 (3-30 microM) counteracted the inhibitory effects of omega-conotoxin GVIA in field-stimulated rat vas deferens.

Animals↗

Contractions induced by grayanotoxin I in the guinea-pig vas deferens.

1 In the guinea-pig vas deferens, grayanotoxin I (G-I), a diterpenic toxin isolated from certain ericaceous plants caused rhythmic contractions which were dose-dependent (5 x 10(-5) M - 10(-3) M); these followed an initial transient contraction.2 The G-I (3 x 10(-4) M)-induced contraction was markedly inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 x 10(-7) M and 10(-6) M) or tetrodotoxin (TTX, 5 x 10(-7) M), but remained almost unaffected by atropine (10(-6) M) or mecamylamine (3 x 10(-5) M). This contraction was also abolished after storage at 4 degrees C for 7 days or incubation in Na-deficient or Ca-free medium.3 After treatment with G-I (3 x 10(-5) M), which did not alter the tension of the preparation, transmural stimulation (10-50 Hz, 0.5 ms, supramaximal voltage, for 3 s) induced a slower contraction (second contraction) following the first rapid contraction caused by stimulation.4 The second contraction was inhibited or abolished by reserpine (2 mg/kg on 2 days), phentolamine (2 x 10(-7) M and 10(-6) M) and TTX (2 x 10(-8) M), but was not affected by atropine (10(-6) M) and mecamylamine (3 x 10(-5) M).5 G-I (3 x 10(-5) M) shifted the dose-response curves for noradrenaline (NA), acetylcholine and high-K contractions to the left in a parallel manner and slightly increased the maximal response to these agonists.6 G-I (3 x 10(-4) M) caused a release of endogenous NA from the vas deferens which was approximately 120 times that of control preparations. This response was inhibited or abolished by TTX (5 x 10(-7) M) or incubation in Ca-free medium.7 These results suggest that the G-I-induced contraction of the vas deferens and the G-I-induced second contraction on electrical stimulation are the result of an indirect action mediated through the release of NA from the adrenergic nerve endings.

Animals↗

Contraception with danazol plus testosterone enanthate in the rabbit. I. Effects on vas deferens.

Effects of danazol plus testosterone enanthate on rabbit vas deferens are investigated. Seminal, biochemical tissue and histological studies were performed. Sperm motility was markedly impaired with the advancement of treatment. At the end of treatment 75 per cent of the animals became azoospermic. Seminal fructose did not change, whereas citric acid showed a progressive non-significant increase. Phosholipid and protein contents of vas deferens decreased during drug exposure. No appreciable changes were observed in sialic acid concentration. Citric acid and fructose in ampullae reduced following 60 days of treatment. Vas deferens lumen was devoid of spermatozoa. The combination therapy impaired the secretory activity of vas deferens reversibly.

Animals↗

Effect of extracellular Mg concentration on electrically induced contractions of rat vas deferens in vitro.

Contraction of smooth muscles of the vas deferens plays an important role in the propulsion of sperm into the pelvic urethra. This study examined the influence of external Mg2+ concentration on reactivity of the rat vas deferens to electrical stimulation in vitro. Vasa deferentia isolated from adult male rats were set up in tissue baths containing physiological salt solution at 37 degrees C and were stimulated electrically. Thereafter, increasing concentrations of Mg2+ were added to the bath and their effects on electrically evoked contractions were recorded. The effect of external Mg2+ depletion on evoked contractions was also examined. External Mg2+ depletion enhanced the contractile response to electrical stimulation while increasing external Mg2+ concentration inhibited the contractions. The inhibitory effect of Mg2+ was partially reversed by increasing extracellular Ca2+ concentration and was not additive with nifedipine. The results indicate that reactivity of the vas deferens to electrical stimulation is modulated by extracellular Mg2+ concentration. The possible relevance of these data to sperm transport through the vas deferens is discussed.

Animals↗

Effects of veratrine and paeoniflorin on isolated mouse vas deferens.

In this study, we attempted to identify the interactions and mechanisms between veratrine and paeoniflorin on isolated mouse vas deferens. Paeoniflorin had no effect on isolated mouse vas deferens. Veratrine (1 x 10(-5) approximately 1 x 10(-3) g/ml) could directly induce contraction of isolated rat and mouse vas deferens. The concentration induced by veratrine (1 x 10(-5) g/ml) was completely inhibited by Ca2+-free solution and verapamil (1 x 10(-5) M), in both the epididymal and the prostatic portions of isolated mouse vas deferens. Naloxone (1 x 10(-5) M) did not alter the contraction induced by veratrine (1 x 10(-5) g/ml) in either the epididymal or the prostatic portions of isolated mouse vas deferens. Paeoniflorin (4.8 x 10(-5) g/ml) inhibited the contraction induced by veratrine (1 x 10(-5) g/ml) in both the epididymal and the prostatic portions of isolated mouse vas deferens. Paeoniflorin (4.8 x 10(-5) g/ml) potentiated norepinephrine (1 x 10(-5) M)-induced phasic contraction in the epididymal portion, but decreased contractions in the prostatic portion. Paeoniflorin (4.8 x 10(-5) g/ml) increased KCI (56 mM)-induced phasic contraction in the epididymal portion, but decreased the tonic contraction in either the epididymal or the prostatic portion. Veratrine (1 x 10(-5) g/ml)-induced contractions could be decreased by pretreatment with ryanodine (1 x 10(-5) M) in both the epididymal and the prostatic portions. Pretreatment with the combination of paeoniflorin (4.8 x 10(-5) g/ml) and ryanodine (1 x 10(-5) M) did not potentiate the inhibition of paeoniflorin in the veratrine-induced contraction in both the epididymal and the prostatic portions of isolated mouse vas deferens.

Animals↗

Distribution of chromogranins A and B and secretogranin II (secretoneurin) in rat pelvic neurons and vas deferens.

The family of chromogranins/secretogranin peptides comprises three major subtypes: chromogranin A, chromogranin B and secretogranin II. We have characterized these proteins in rat vas deferens and pelvic ganglia by using two approaches. Firstly, extracts of rat vas deferens were subjected to molecular sieve chromatography followed by radioimmunoassay. The results indicate that, in the peripheral nerves of this organ, chromogranin B and secretogranin II are processed to small peptides, i.e. PE-11 and secretoneuron, respectively. Secondly, we investigated the localization of each of these peptides in the rat pelvic ganglia and vas deferens. Comparisons with the distribution of tyrosine hydroxylase, choline acetyltransferase, vesicular acetylcholine transporter and SV2 were carried out in double labelling studies. All tyrosine hydroxylase-positive neurons contained neuropeptide Y, but many neuropeptide Y-containing neurons were negative for tyrosine hydroxylase. In the pelvic ganglia, chromogranin A was widely localized in the neuropeptide-positive neurons and 65% of chromogranin A-containing neurons were positive for tyrosine hydroxylase, suggesting their adrenergic nature. However, in nerve terminals of the vas deferens, chromogranin A was present at very low, or undetectable, levels. The chromogranin B-derived peptide PE-11, on the other hand, was absent from the large-sized, tyrosine hydroxylase-positive neurons, but present in some small-sized neurons that were choline acetyltransferase/vesicular acetylcholine transporter-positive and tyrosine hydroxylase-negative. In the vas deferens, PE-11 was present with intense immunoreactivity in nerve terminals of the lamina propria beneath the epithelium, but it was very sparse in the muscular layer and co-localized with vesicular acetylcholine transporter-like immunoreactivity, suggesting a cholinergic nature. The secretogranin II-derived peptide secretoneurin was distributed with strong immunoreactivity in the somata of pelvic ganglion neurons, 72% of which also contained tyrosine hydroxylase, as well as in nerve terminals in the muscular layer and the lamina propria of the vas deferens. Most, if not all, secretoneurin-positive terminals in the pelvic ganglia and the vas deferens were positive for choline acetyltransferase/vesicular acetylcholine transporter-like immunoreactivity. Retrograde tracing with FluoroGold demonstrated that the majority of FluoroGold-labelled neurons in the pelvic ganglia were positive for either chromogranin A or secretoneurin. The present study indicates that chromogranins A and B and secretogranin II are proteolytically processed to a high degree in the nerves of the rat vas deferens. Furthermore, they are heterogeneously localized in subsets of neurons of the pelvic ganglia and in different sets of nerve terminals in the vas deferens, suggesting that each of these peptides may play distinct roles in neurons of the autonomic nervous system to the vas deferens.

Animals↗

A 77-base pair LINE-like sequence elicits androgen-dependent mvdp/akr1-b7 expression in mouse vas deferens, but is dispensable for adrenal expression in rats.

Mvdp/akr1-b7 (mouse vas deferens protein/aldo-keto reductase 1-B7) encodes an enzyme responsible for detoxification of a steroidogenesis byproduct. MVDP/AKR1-B7 is expressed in both rat and mouse adrenal cortex under ACTH control, whereas strong androgen-dependent accumulation in the vas deferens is mouse specific. Comparison of the regulatory regions of the two orthologs reveals a strong identity, disrupted by acquisition of a 77-bp LINE-derived sequence in the mouse promoter. Although ACTH responsiveness is observed in both species, the absence of this 77-bp sequence in the rat is associated with changes in transcription initiation sites. Transfection studies demonstrate that the CCAAT/enhancer-binding protein and selective promoter factor 1-binding sites previously shown to be essential for cAMP/ACTH induction in the mouse are consequently dispensable in the rat. Our data support the idea that the most striking change generated by this acquisition is the strong, androgen-dependent, vas deferens expression observed in mouse. 1) In rat vas deferens, rakr1-b7 expression is barely detectable and is not androgen sensitive. 2) Androgen receptor binds efficiently to an androgen response element within the 77-bp mouse-specific element. 3) Its insertion confers androgen sensitiveness to rakr1-b7 regulatory regions in an androgen response element-dependent manner in transient transfections. We propose that this acquired androgen-responsive region may be responsible for vas deferens androgen-regulated gene expression in vivo.

Adrenal Glands↗

Zinc and copper content in rat epididymis and vas deferens.

The zinc and copper content in the different epididymal segments and vas deferens of castrated rats were investigated with the help of atomic absorption spectrophotometer. The vas deferens showed maximum zinc content as compared to that of different parts of epididymis in all groups whether castrated unilaterally, bilaterally or in the intact control. Zinc content was reduced in the epididymis and vas deferens ipsilateral to the castrated side as compared to that of contralateral control and intake animals. Lowest zinc content was observed in the epididymis and vas deferens of bilaterally castrated animals from that of other groups. Absence of sperms was observed in all segments of epididymis and vas in bilaterally castrated animals and from the unilaterally castrated side. Copper content was unaltered in all epididymal segments and vas deferens. There appears to be a correlation between the absence of sperms in the male genital tract and the decrease in zinc content.

Animals↗

Sympathectomy reveals alpha 1A- and alpha 1D-adrenoceptor components to contractions to noradrenaline in rat vas deferens.

We have previously demonstrated that contractions of rat vas deferens to exogenous noradrenaline involve predominantly alpha(1A)-adrenoceptors, but that contractions to endogenous noradrenaline involve predominantly alpha(1D)-adrenoceptors. In this study, we have examined the effects of sympathectomy on the subtypes of alpha(1)-adrenoceptor in rat vas deferens in radioligand binding and functional studies. In vehicle-treated tissues, antagonist displacement of [(3)H]prazosin binding to alpha(1)-adrenoceptors was consistent with a single population of alpha(1)-adrenoceptors. Binding affinities for a range of alpha(1)-adrenoceptor antagonists were expressed as pK(i) values and correlated with known affinities for alpha(1)-adrenoceptor subtypes. The correlation was significant only with alpha(1A)-adrenoceptors. In tissues from rats sympathectomised with 6-hydroxy-dopamine (2 x 100 mg kg(-1) i.p.), binding affinity for the alpha(1D)-adrenoceptor antagonist BMY 7378 fitted best with a two-site model. In functional studies, the potency of noradrenaline at producing total (phasic plus tonic) but not tonic contractions was increased in tissues from sympathectomised rats. Results obtained from sympathectomised rats suggest that phasic contractions are mainly alpha(1D)-adrenoceptor mediated, whereas tonic contractions are mainly alpha(1A)-adrenoceptor mediated, based on the effects of BMY 7378 and the alpha(1A)-adrenoceptor antagonist RS 100329. It is concluded that the predominant alpha(1)-adrenoceptor in vehicle-treated rat vas deferens is the alpha(1A)-adrenoceptor, both in terms of ligand binding and contractions to exogenous agonists. The alpha(1D)-adrenoceptor is only detectable by ligand binding following chemical sympathectomy, but is involved in noradrenaline-evoked contractions, particularly phasic contractions, of rat vas deferens.

Adrenergic alpha-1 Receptor Antagonists↗

The effect of denervation of the cyclic nucleotides levels of the vas deferens.

We measured the cyclic nucleotides in levels of the rat vas deferens surgically denervated in order to investigate the relationship between denervation supersensitivity and cyclic nucleotides. Two days after denervation, cyclic AMP slightly decreased to 90.4% of control and cyclic GMP also decreased but not significantly. So it is assumed that almost all of the cyclic nucleotides are not neurogenic but myogenic. When the rat vas deferens was incubated with l-norepinephrine 10(-4) for 3 min, the cyclic GMP level in the vas deferens denervated for seven d was significantly higher than that in the intact specimen, and the cyclic AMP level in the intact one was almost the same as in the denervated preparation. Denervation produced leftward shift of the dose response curve in cyclic GMP level to l-norepinephrine. After incubation with acetylcholine (10(-4)M), however, cyclic GMP and cyclic AMP levels in the denervated vas deferens were almost the same as in the intact one. Therefore, it is suggested that cyclic nucleotides don't relate to the induction of nonspecific supersensitivity by denervation in the rat vas deferens.

Acetylcholine↗

Effect of temperature reduction on the vas deferens hyperresponsiveness of sensitized mice.

1. The present study was designed to investigate the effect of active sensitization on the responsiveness of mouse vas deferens before and after moderate cooling. Contractile responses to noradrenaline (NA) were isometrically recorded in the vas deferens of control and ovalbumen-sensitized mice at 37 degrees C and 22 degrees C. 2. Enhancement of the vas deferens reactivity to NA was observed in the sensitized vs control mice at 37 degrees C and 22 degrees C (P < 0.01). In sensitized mice, maximal contraction was significantly increased compared with controls, and sensitization-induced hyperresponsiveness was greater at 22 degrees C compared with 37 degrees C. At 37 degrees C, contractile responses to barium chloride were significantly enhanced in the sensitized mice compared with controls, whereas the reduction of the temperature to 22 degrees C produced a marked inhibition of vas deferens contractions in both groups. Caffeine-induced contractions of the vas deferens were similar in control and sensitized mice at 37 degrees C. After moderate cooling to 22 degrees C, vas deferens from sensitized mice became hyperresponsive compared with controls. 3. Ouabain (0.1 mM) produced an increase of NA-induced contraction in control and sensitized vas deferens at 37 degrees C (P < 0.01). It had no significant effect in the control at 22 degrees C but produced a marked inhibition of NA-induced contraction in the sensitized vas deferens at 22 degrees C. Contractions to NA in the presence of vanadate (1 mM) were depressed in control and sensitized mice at both temperatures. 4. These results suggest that sensitization-induced hyperresponsiveness of the mouse vas deferens is mediated by an increased mobilization of intracellular calcium. The involvement of an unknown ouabain-sensitive pathway in sensitization-induced alterations is also discussed.

Analysis of Variance↗