The effects of denervation, cocaine, 6-hydroxydopamine and reserpine on the characteristics of drug-induced contractions of the depolarized smooth muscle of the rat and guinea-pig vas deferens

Previous studies have suggested that postjunctional supersensitivity of the vas deferens is due in part to altered electrophysiological properties, the sensitivity of the muscle being increased to any agonist which initiates contraction by means of depolarizing the cell membrane. Results of the present study indicate that altered electrical properties are not the only postjunctional changes which can account for the enhanced response. Dose-response curves for stimulant agonists were obtained in isolated vasa deferentia which were depolarized by a K-rich, Na-free solution. Chronic denervation resulted in a 2- to 3-fold displacement of the dose-response curve for norepinephrine to the left of control. Cocaine (10-(5)M) did not potentiate the response to norepinephrine of the innervated, depolarized smooth muscle. Supporting the contention that the supersensitivity of the depolarized tissue is postjunctional in nature was the finding that the denervated vas deferens was supersensitive to methoxamine, an agent which is not taken up by the neuronal amine transport system. Pretreatment of rats with reserpine (1.0 mg/kg/day for 5-7 days) also produced supersensitivity of the depolarized vas deferens. The increased maximal response to drugs of the denervated rat vas deferens which is observed in normally polarized tissues is absent in depolarized tissues suggesting that the phenomenon of increased maximum requires the existence of a membrane potential in order to be manifest. The denervated vas deferens, but not the vas deferens from reserpine-pretreated animals, exhibits an increase in the duration of drug-induced contractions. This effect occurs in both normal and depolarizing salt solutions suggesting that the change which leads to this phenomenon differs from those alterations which lead to postjunctional supersensitivity and to the enhanced maximal response.     

Defining the precapillary sphincter

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.     

Vas deferens desensitization by noradrenaline and other drugs

Desensitization of the isolated rat vas deferens was demonstrated by using noradrenaline, 5-hydroxytryptamine, carbachol, acetylcholine or barium chloride as a test concentration after a large concentration (concentration producing a contraction that was 80% of the maximum) of the same agonist. The large concentration of noradrenaline caused desensitization in response to 5-hydroxytryptamine and acetylcholine but not to carbachol and barium chloride. Desensitization is not altered by reserpine--in pretreatment of rats with reserpine or reserpine in Tyrode solution--imipramine and 6-hydroxydopamine. Surgical denervation or modification of the sodium and calcium concentration of the Tyrode solution did not either alter desensitization. Results show that in the rat isolated vas deferens desensitization is not mediated by an action of noradrenaline on the adrenergic neuron.     

KCl contractions in the rat intact and bisected vas deferens: contribution of endogenous noradrenaline release

1. KCl produced a biphasic contraction in the intact rat vas deferens. Both components were larger and the initial rapid phasic component was faster in the prostatic portion than the epididymal portion. In some experiments the epididymal phasic response was a single slow contraction, while in others it had a mixture of fast and slow responses. 2. Phentolamine reduced the phasic response but not the tonic response of the intact vas deferens. This effect was not observed after denervation produced by chronic guanethidine treatment. 3. Both phases of the response to KCl 160 mmol/l were substantially reduced by phentolamine in the epididymal portion. In the prostatic portion phentolamine produced only slight inhibition of the phasic component and had no effect on the tonic component. 4. Isoprenaline had no effect on the response to KCl 160 mmol/l but reduced both phases of the response to KCl 50 mmol/l. This effect was antagonized by propranolol. 5. It is concluded that part of the phasic component of the response to KCl in the rat vas deferens is due to the release of noradrenaline from intramural nerves.     

Effects of chronic bretylium treatment on the sympathetic neuron and the smooth musculature of the rat

The effects of chronic i.p. injection of high doses of bretylium on sympathetic nerves on the smooth musculature of the vas deferens of adult and newborn rats were examined using fluorescence histochemistry, light and electron microscopy and organ bath physiological techniques. Bretylium treatment caused mitochondrial swelling, loss of cristae and the formation of electron-dense inclusions in the mitochondria of sympathetic neurons. However, neuron degeneration was not observed and fluorescent histochemical appearance of adrenergic neurons was normal. A small transient supersensitivity of the isolated vas deferens of bretylium-treated rats to noradrenaline, but not to acetylcholine, occurred. There was, however, considerable increase in the maximal contractile response to both noradrenaline and acetylcholine. In high calcium concentrations acetylcholine-induced contractions of vasa deferentia from bretylium-treated rats were significantly greater than control; there was no difference in magnitude of noradrenaline-induced contractions.     

Activities and androgenic regulation of kreb cycle enzymes in the epididymis and vas deferens of rhesus monkey

The activities of nine enzymes of the TCA cycle were estimated in the initial segment, caput, corpus and cauda segments of epididymis and vas deferens of adult rhesus monkey and expressed as units per mg DNA. These enzymes were also estimated in epididymal segments and vas deferens of castrated and castrated-androgen replaced monkeys as well. Results indicated higher activities of most of the enzymes in vas deferens as compared to epididymal segments. All the enzymes showed marked reduction in epididymis and vas deferens after castration, the effect being much more pronounced in the epididymis, than in the vas. Androgen replacement in castrated monkeys stimulated most of the enzymes markedly in epididymis and in the vas deferens as compared to their castrated values. The response of cauda and vas deferens to exogenous androgen treatment was however moderate, as compared to the other epididymal segments. The studies indicate that energy metabolism in the epididymis (as well as in the vas deferens) is strictly androgen dependent and the energy charge of these target organs is likely to fall appreciably after castration, which may in turn affect many energy dependent processes of these organs (e.g. absorption, secretion of specific substances etc.) which have been considered important for sperm maturation and survival.     

A1 adenosine receptor modulation of electrically-evoked contractions in the bisected vas deferens and cauda epididymis of the guinea-pig

1. The effects of adenosine receptor agonists upon both electrically-evoked and phenylephrine-induced contractile responses were investigated in the bisected vas deferens and the cauda epididymis of the guinea-pig. Electrical field-stimulation (10 s trains of pulses at 9 Hz, 0.1 ms duration, supramaximal voltage) elicited biphasic and monophasic contractile responses from preparations of bisected vas deferens and cauda epididymis, respectively; these responses were abolished by tetrodotoxin (300 nM). 2. In the prostatic half of the vas deferens the A1 selective adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and (2S)-N6-[2-endo-norbornyl]adenosine ((S)-ENBA) and the non-selective A1/A2 adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) inhibited electrically-evoked contractions (pIC50+/-s.e.mean values 6.15+/-0.24, 5.99+/-0.26 and 5.51+/-0.24, respectively). The responses to CPA were blocked by the A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine, DPCPX (100 nM). 3. In the epididymal half of the vas deferens NECA potentiated (at < or = 100 nM) and inhibited (at > or = 1 microM) electrically-evoked contractions. In the presence of the non-selective alpha-adrenoceptor antagonist phentolamine (3 microM), the alpha1-adrenoceptor antagonist, prazosin (100 nM), or at a reduced train length (3 s) NECA inhibited electrically-evoked contractions (pIC50 values 6.05+/-0.25, 5.97+/-0.29 and 5.71 +/-0.27, respectively). CPA (at 10 microM) also inhibited electrically-evoked contractions in this half of the vas deferens. In the presence of prazosin (100 nM), CPA also inhibited electrically-evoked contractions (pIC50 6.14+/-0.67); this effect was antagonized by DPCPX (30 nM, apparent pK(B) 8.26+/-0.88). In the presence of the P2 purinoceptor antagonist, suramin (300 microM), CPA (up to 1 microM) potentiated electrically-evoked contractions. 4. NECA, CPA and APNEA potentiated electrically-evoked contractions in preparations of cauda epididymis (pEC50 values 7.49+/-0.62, 7.65+/-0.74 and 5.84+/-0.86, respectively), the response to CPA was competitively antagonized by DPCPX (100 nM) with an apparent pK(B) value of 7.64+/-0.64. 5. The alpha1-adrenoceptor agonist phenylephrine elicited concentration-dependent contractile responses from preparations of bisected vas deferens and cauda epididymis. NECA (1 microM) potentiated responses to phenylephrine (< or = 1 microM) in the epididymal, but not in the prostatic half of the vas deferens. In preparations of epididymis NECA (1 microM) shifted phenylephrine concentration response curves to the left (4.6 fold). In the presence of a fixed concentration of phenylephrine (1 microM), NECA elicited concentration-dependent contractions of preparations of the epididymal half of the vas deferens and of the epididymis (pEC50 values 7.57+/-0.54 and 8.08+/-0.18, respectively). NECA did not potentiate responses to ATP in either the epididymal half of the vas deferens or the epididymis. 6. These studies are consistent with the action of stable adenosine analogues at prejunctional A1 and postjunctional A1-like adenosine receptors. The prejunctional A1 adenosine receptors only inhibit the electrically-evoked contractions of purinergic origin (an effect predominant in the prostatic half of the vas deferens). At the epididymis, where electrically-evoked contractions are entirely adrenergic, the predominant adenosine receptor agonist effect is a potentiation of alpha1-adrenoceptor-, but not of ATP-induced contractility.     

Nitric oxide synthase is co-localized with vasoactive intestinal polypeptide in postganglionic parasympathetic nerves innervating the rat vas deferens

Cross-sections of the vas deferens taken from control adult male rats showed positive histochemical reactivity to acetylcholinesterase and immunoreactivity for antibodies to protein gene product 9.5, tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, nitric oxide synthase and calcitonin gene-related peptide. Immunoreactivity to substance P was very sparse. Histochemical reactivity to acetylcholinesterase and immunoreactivity to vasoactive intestinal polypeptide and nitric oxide synthase was concentrated in the subepithelial lamina propria and inner smooth muscle layers. Complete surgical denervation resulting from transection of the nerve arising from the pelvic ganglion which supplies the vas deferens totally abolished the immunoreactivity to all of the antibodies tested as well as the histochemical reactivity to acetylcholinesterase. In sections of the prostatic end of the vas deferens taken from rats neonatally pretreated with capsaicin, immunoreactivity to calcitonin gene-related peptide and substance P was reduced by 75 and 83%, respectively. Immunoreactivity to neuropeptide Y, vasoactive intestinal polypeptide and nitric oxide synthase was similar in tissue sections taken from capsaicin-treated rats and those taken from control tissues. Pretreatment of rats with guanethidine or 6-hydroxydopamine decreased immunoreactivity to tyrosine hydroxylase and neuropeptide Y by 60-70%, but immunoreactivity to substance P, vasoactive intestinal polypeptide and nitric oxide synthase was unchanged, while immunoreactivity to calcitonin gene-related peptide and acetylcholinesterase staining was increased by guanethidine but not by 6-hydroxydopamine treatment. Triple labelling experiments showed nitric oxide synthase, vasoactive intestinal polypeptide and acetylcholinesterase all to be co-localized in some nerve fibres. These results indicate that the nitric oxide synthase contained in the nerve fibres innervating the rat vas deferens is unaffected by pretreatment of rats with capsaicin, 6-hydroxydopamine or guanethidine but is abolished by surgical denervation, of postganglionic parasympathetic, sympathetic and sensory nerves. Therefore it appears that nitric oxide synthase is co-localized with vasoactive intestinal polypeptide in the postganglionic parasympathetic nerves which innervate the rat vas deferens.     

Blood blisterlike aneurysms of the internal carotid artery

1. The effects of ryanodine, procaine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on noradrenaline (NA)- and caffeine-induced contractions of human vas deferens were investigated. 2. In the presence of nifedipine (1 microM), NA ( 100 microM) evoked biphasic contractions. Caffeine (20 mM) evoked repeatable tonic contractions. 3. Ryanodine (30 microM) inhibited the initial but not the secondary component of NA contractions. Procaine (1 and 10 mM) inhibited both components. Contractions induced by caffeine were unaffected by ryanodine or procaine. 4. The calmodulin antagonist W-7 (100 microM) reduced, in a reversible manner, both components of NA-induced response. Caffeine-induced contractions were also reduced in most preparations (8 of 11). In all preparations, contractions induced by caffeine were markedly inhibited after the washout of W-7. Higher doses of W-7 (300 microM) induced an increase in basal tension. 5. These results indicate that NA contracts the longitudinal muscle of human vas deferens by a ryanodine-sensitive calcium-induced calcium release (CICR) mechanism and, in addition, a ryanodine-insensitive pathway: both are sensitive to procaine. In contrast, contraction induced by caffeine is mediated by a pathway that is atypically insensitive to either ryanodine or procaine. The sensitivity of NA- and caffeine-induced contraction to W-7 suggests a role for calcium and its interaction with calmodulin in the response to both agents. The paradoxical action of W-7 is discussed.     

Tetrodotoxin-sensitive action potentials in smooth muscle of mouse vas deferens

Action potentials were recorded during impalements of some but not all smooth muscle cells of mouse vas deferens in response to both nerve stimulation and intracellular current injection. They were resistant to blockade by nifedipine (0.1-1.0 microM) but were blocked by tetrodotoxin (TTX, 0.2-1.0 microM) when this was added in the presence of nifedipine. It is suggested that voltage-dependent sodium (Na+) channels are present in mouse vas deferens that function to amplify calcium (Ca2+) influx through voltage-dependent Ca2+ channels.     

Inhibition of purinergic transmission by prostaglandin E1 and E2 in the guinea-pig vas deferens: an electrophysiological study

1. The effects of prostaglandin E1 (PGE1) and E2 (PGE2) on postjunctional electrical activity in the guinea-pig vas deferens evoked by sympathetic nerve stimulation were investigated using both intracellular and focal extracellular recording techniques in vitro. 2. Bath application of PGE1 (1-100 nM) or PGE2 (0.1-100 nM) concentration-dependently inhibited the amplitudes of all excitatory junction potentials (e.j.ps) evoked during short trains of stimuli (10 stimuli at 1 Hz). Increasing the duration of nerve stimulation (100 stimuli at 1 Hz) did not overcome this inhibitory effect. At these concentrations PGE1 and PGE2 were without any apparent inhibitory effect on the amplitudes of spontaneous e.j.ps. 3. Local application of PGE1 (10-100 nM) or PGE2 (10-30 nM) markedly reduced the frequency of occurrence of excitatory junction currents (e.j.cs) evoked by trains of 20-100 stimuli at 1 to 4 Hz without changing the amplitudes of spontaneous e.j.cs or the configuration of the nerve terminal impulse. 4. In the presence of PGE1 or PGE2, raising the frequency of stimulation (from 1 to 4 Hz), increased the likelihood of e.j.c. occurrence. 5. The postjunctional electrical activity recorded in the guinea-pig vas deferens is believed to be due to ATP released from the sympathetic nerve endings. Thus the present study demonstrates that both PGE1 and PGE2 powerfully inhibit quantal ATP release in the guinea-pig vas deferens.     

Relation between image-based assessment of distal radius trabecular structure and compressive strength

This study was undertaken to explore the spinal cord segments controlling the canine and human vas deferens and differentiation of the mammalian sympathetic pathways to the vas deferens. Thoracolumbar white communicating rami (WCR) were electrically stimulated in the dogs. Stimulation of the 1st, 2nd, 3rd, and 4th lumbar WCR elicited an elevation of intraluminal pressure of the vas deferens in 2, 10, 16, and 14 of 20 dogs examined, respectively, whereas stimulation of sympathetic chain (between the 13th thoracic and 1st lumbar ganglia), 13th thoracic WCR, intermesenteric plexus, and 5th lumbar WCR showed no response in any of the 10, 2, 12, and 5 dogs examined, respectively. Anatomical study of the 118 human lumbar splanchnic nerves of 55 cadavers showed that almost all lumbar splanchnic nerves (96%) originated from L2 and/or L3 sympathetic chain ganglia (L1-2 spinal cord levels). Comparative anatomical study of the mammalian sympathetic pathways to the vas deferens showed that the caudal mesenteric plexus is not divided in rats, rabbits, cats, and dogs and is partially divided into two plexuses in monkeys and completely in humans and that separation of the sympathetic component in the pelvic nerve (isolation of the sacral splanchnic nerve) is in progress in the primate. These results indicate that spinal cord segments controlling the vas deferens are L1-4 in the dog and probably L1-2 in humans and that differentiation of the sympathetic nerve pathways is proceeding at both main and compensatory pathways to the vas deferens in the primate.     

Congenital absence of the vas deferens: incomplete penetrance of cystic fibrosis gene mutations

PURPOSE: We evaluated the penetrance of cystic fibrosis gene mutations for the clinical phenotype of congenital bilateral absence of the vas deferens. MATERIALS AND METHODS: We retrospectively reviewed the fertility status of 244 brothers of 105 men with congenital bilateral absence of the vas deferens. Testing for the most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and for haplotype analysis of the intron 8/polythymidine segment was recommended for all men with congenital bilateral absence of the vas deferens. RESULTS: Of 244 brothers of men with congenital bilateral absence of the vas deferens 131 were eligible for assessment of fertility. Of the 131 evaluable brothers only 7 (5%) were found to have congenital bilateral absence of the vas deferens. This prevalence is 5 times lower than that predicted for congenital bilateral absence of the vas deferens (25%) based on the autosomal recessive inheritance pattern seen in classical cystic fibrosis. For couples in which the man has congenital bilateral absence of the vas deferens and the female partner tests negative for standard CFTR gene mutations including 5T analysis, the maximum risk of having a child with congenital bilateral absence of the vas deferens is less than 1.0%. CONCLUSIONS: Our data are consistent with incomplete penetrance for the congenital bilateral absence of the vas deferens phenotype after inheritance of cystic fibrosis gene mutations, even after adjusting for environmental factors and wolffian anomalies. Incomplete penetrance may account for a low prevalence of congenital bilateral absence of the vas deferens in the population and may lower the risk of having a child with congenital bilateral absence of the vas deferens for couples undergoing sperm retrieval and assisted reproductive techniques.     

Noradrenaline and ATP: cotransmitters and neuromodulators

Adenosine 5'-triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic nerves supplying the vas deferens and a number of blood vessels. ATP is responsible for the excitatory junctional potentials (EJPs) in response to single nerve impulses and the initial twitch responses of the smooth muscle, while NA produces the longer-lasting tonic contractions. The proportions of ATP to NA vary between different sympathetic nerves; they also change during development and in some pathological conditions, including hypertension. Prejunctional neuromodulation of release of the two cotransmitters appears to involve independent mechanisms and is frequency dependent; this raises the question of whether ATP and NA are stored in separate vesicles or whether there are subpopulations of sympathetic nerves with a predominance of ATP or NA. ATP and NA have synergistic postjunctional actions, whether excitatory (as in the vas deferens and most blood vessels) or inhibitory (as in rabbit coronary vessels). It is suggested that use of the term 'adrenergic nerves' as a synonym for sympathetic nerves is no longer appropriate, although 'adrenergic transmission' or 'purinergic transmission' are still useful terms.     

Effects of cobalt or nickel on the sympathetically mediated contractile responses in rat-isolated vas deferens

Subchronic (30 days) exposure of rats to Co(NO3)2 or NiSO4 (20 mg.kg-1) in drinking water caused suppression of the isolated vas deferens contractile responses to exogenous adenosine 5'-triphosphate (ATP), noradrenaline, and l-phenylephrine, shifting the concentration-response curves to the relevant agonist to the right. Both metals facilitated the alpha 1-adrenoceptor antagonistic effects of prazosin, which resulted in increased pA2 values for the drug (9.68 +/- 0.13 in controls vs. 10.15 +/- 0.12 in Co(2+)-treated preparations and 12.60 +/- 0.67 in Ni(2+)-treated preparations). The inhibitory effect of clonidine on the contractions in response to low-frequency electrical field stimulation (EFS) in metal-treated preparations was decreased with pD2 values: 10.52 +/- 0.04 in controls, 9.56 +/- 0.13 in Co(2+)-treated preparations and 9.92 +/- 0.16 in Ni(2+)-treated preparations. The monophasic contractile responses to low-frequency EFS (0.1 Hz, 1 ms, 80 V) as well as the first phase of the biphasic contractions after high-frequency long-lasting EFS (300 pulses, 0.1 ms, 40 V, at 4, 8 or 20 Hz) were significantly increased in both groups of heavy metal-treated preparations. Therefore, subchronic exposure to Co2+ or Ni2+ leads to changes in pre- and postjunctional mechanisms underlying the sympathetically mediated contractile activity of isolated rat vas deferens.     

Autoinhibition, sympathetic cotransmission and biphasic contractile responses to trains of nerve stimulation in the rodent vas deferens

1. The present review critically discusses the evidence for and against the various hypotheses that have been proposed to explain the biphasic contractile response of the rodent vas deferens to trains of electrical field stimulation (EFS). 2. It is widely accepted that the initial component of the biphasic response of the rodent isolated vas deferens to trains of EFS is mediated by ATP and the second slower tonic contractions is mediated by noradrenaline (NA). This theory is based on the ability of antagonists of the post-junctional receptors for these neurotransmitters to inhibit the respective components of the biphasic response and on the ability of exogenous application of either ATP or NA to mimic the responses of each phase. 3. Prejunctional autoinhibition has also been proposed as the cause of the biphasic response. This is based primarily on the ability of alpha 2-adrenoceptor antagonists to transform responses from biphasic to monophasic and on the ability of neuronal NA uptake inhibitors to accentuate the separation of the two phases. 4. Atypical or extrajunctional NA receptors have also been proposed to be the mediators of the component of the response to nerve stimulation that is resistant to the traditional alpha-adrenoceptor antagonists. 5. Different contractile mechanisms and/or sources of calcium have also been postulated to cause the biphasic response. Blockers of intracellular Ca2+ mobilization are able to block the initial component, while blockers of extracellular Ca2+ entry inhibit the second tonic phase. 6. It is concluded that because alpha 1-adrenoceptor antagonists and blockers of P2 purinoceptors have also been shown to block both phases of the response to trains of EFS, prejunctional auto-inhibitory mechanisms perhaps provide the most sound explanation for the phenomenon of the biphasic contractile response to trains of EFS.     

Changes in electrophysiological properties and noradrenaline response in vas deferens of diabetic rats

The purpose of this study was to study changes in the sympathetic nerves of the vas deferens in 10-week-old streptozotocin-induced diabetic rats. To assess the activity of autonomic neurons, we recorded the amplitude and frequency of spontaneous junction potentials in vasa deferentia from age-matched controls and streptozotocin-induced diabetic rats. No change in the resting membrane potential of the smooth muscle of the vas deferens was found in streptozotocin-induced diabetic rats. The frequency of spontaneous junction potentials was significantly increased in the streptozotocin-induced diabetic rats and their amplitude was also markedly increased. The dose-response curve for the contractile response of the vas deferens to noradrenaline was significantly shifted to the right and the apparent affinity (pD2 value) was significantly decreased in streptozotocin-induced diabetic rats. These results suggest that degeneration of sympathetic neurons may occur in the vas deferens of 10-week streptozotocin-induced diabetic rats and that the greater amplitude of the spontaneous junction potentials may be related to an increase in Ca2+ mobilization, though the increase in Ca2+ mobilization does not lead to an enhanced contractile response.     

The role of acetylcholine receptors and acetylcholinesterase activity in the development of denervation supersensitivity

Strips of muscle from innervated and denervated rat hemidiaphragm were tested for sensitivity to acetylcholine and to carbachol. For both agonists, denervation (6-8 days) produced notable supersensitivity. However, the increase in sensitivity to acetylcholine (ca. 600-fold) was much greater than that to carbachol (ca. 51-fold). Denervation also produced an increase in [3H]alpha-bungarotoxin binding (ca. 20-fold), presumably indicative of an increase in the number of acetylcholine receptors. In addition to causing increases in tissue sensitivity and receptor number, denervation caused a marked loss of acetylcholinesterase activity (ca. 70%) and a modest loss of butyrylcholinesterase activity (ca. 20%). When innervated muscle was pretreated with eserine (5 X 10(-5) M), there was a loss of acetylcholinesterase activity (ca. 86%) and butyrylcholinesterase activity (ca. 36%). Simultaneously, there was an increase in tissue sensitivity to acetylcholine (ca. 26-fold). When denervated muscle was pretreated with eserine, there was no loss of enzyme activity beyond that caused by denervation. Furthermore, eserine pretreatment did not increase denervated muscle sensitivity to acetylcholine. The data suggest that both an increase in acetylcholine receptors and a decrease in acetylcholinesterase activity contribute to the phenomenon of denervation supersensitivity.     

Studies on the neurophysiology of the vas deferens

In order to investigate the mechanism of sperm transport along the genital ducts, intraluminal pressure of isolated segments of the vas deferens was recorded in vivo. Responses to filling and mechanical as well as pharmacologic and electric stimulation of the autonomic nervous system were monitored. Contraction waves were initated in response to the stretch of filling and from mechanical stimulation. Pharmacologic response was variable. Low doses of alpha-adrenergic stimulant produced an increase in frequency of the contraction wave. Large doses of the same drug induced stroking contraction of the entire vas. alpha-Blocking drugs did not alter the rhythmic activity of the vas. beta-Adrenergic stimulation blocked peristaltic activity while administration of parasympathomimetic drugs increased the force of contraction. Electric stimulation of the hypogastric nerve produced strong sustained contractions. These data suggest that, whenever stretched, the vas deferens responds by regular peristaltic waves of low amplitude. These peristaltic waves can be enhanced by sympathomimetics or electric stimulation of the sympathetic system. The contents of the vas are propulsed into the urethra through strong rhythmic contractions of the entire vas.