[Effect of hyperbaric oxygen therapy on antioxidant capacity in brains of rats after acute carbon monoxide poisoning].

OBJECTIVE: This study was designed to observe the antioxidant effects of hyperbaric oxygen (HBO) on brains of rats after acute carbon monoxide (CO) poisoning. METHODS: Sixty-six Sprague-Dawley (SD) male rats were divided into three groups including control group, CO group and HBO group.Morris water maze experiments were used for monitoring cognitive function.Antioxidant capacities were evaluated by detecting T-AOC, GSH-PX, GR and CAT activities in the brain. RESULTS: Compared with the control group (45±17, 43±14, 35±12, 34±11, 29±13) s and the HBO group (40±10, 39±6, 35±9, 31±11, 21±10) s, the CO group (57±5, 54±8, 52±8, 52±10, 46±8) s had the longer escape latency (P<0.05). Compared with the control group (51±6) s and the HBO group(40±10) s, the CO group (8±5) s had the shorter swimming time in I quadrant (P<0.05). Compared with the control group (1.25±0.40) U/mg and the HBO group(0.97±0.31, 0.97±0.39, 1.45±0.15, 1.40±0.25, 1.20±0.20) U/mg, the CO group (0.68±0.09, 0.45±0.17, 0.71±0.18, 0.69±0.29, 0.48±0.29) U/mg had the lower T-AOC activity of brain tissue.The GSH-PX activity (42±13, 106±46, 197±49, 173±42, 429±58) U/mg in the CO group decreased compared with the control group (182±53) U/mg and the HBO group (203±63, 325±86, 389±29, 385±100, 453±32) U/mg.GR activity (4.3±0.7, 2.6±0.5, 3.0±1.2, 1.8±0.8, 3.2±1.9) U/mg in the CO group decreased compared with the control group(14.5±3.0) U/mg and the HBO group (13.9±3.3, 4.3±1.0, 3.9±0.7, 4.8±0.9, 4.6±0.9) U/mg.CAT activity (1.6±0.8, 4.3±1.6, 3.9±1.0, 8.5±2.6, 5.4±1.7) U/mg in the CO group decreased compared with the control group(5.2±1.3) U/mg and the HBO group (5.2±2.2, 8.8±2.8, 5.3±1.0, 9.2±2.1, 14.1±3.8) U/mg. CONCLUSIONS: HBO can improve the behavior of rats after acute CO poisoning.The antioxidant capacity in rat brain tissue after acute CO poisoning decreases, while after the HBO therapy, the antioxidant capacity in rat brain tissue can increase.

Regional specificity of adaptation change in large elastic arteries of simulated microgravity rats.

This study was designed to test the hypothesis that a medium-term simulated microgravity by tail-suspension (SUS) induces hypertrophic and atrophic changes in the common carotid artery and abdominal aorta with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the differential remodeling of the two kinds of large arteries by examining the gene and protein expression of angiotensinogen (AO) and angiotensin II receptor type 1 (AT1R) and their localization in the vessel wall. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. Irrespective of the nature of remodeling, the most prominent changes were in the innermost layers. Immunohistochemistry, in situ hybridization, Western blot, and real time quantitative PCR analysis revealed that SUS induced an up- and down-regulation in AO and AT1R expression in the common carotid artery and abdominal aorta, respectively. In conclusion, our findings have demonstrated some special features in the structural adaptation of large elastic arteries due to a medium-term simulated microgravity.

Fos protein expression in the medulla oblongata and changes in size of spinal lateral horn neurons after 4-wk simulated weightlessness in rats.

Responses of the neurons in medulla oblongata and C8-T1 spinal cord lateral horn of rats induced by simulated weightlessness were investigated using anti-Fos protein and anti-tyrosine hydroxylase (TH) double staining immunohistochemical methods, and Nissl-staining technique respectively. After four weeks of tail-suspension, many Fos-like positive neurons were localized in the medullary visceral zone (MVZ), predominantly in the nucleus of tractus solitarii and ventrolateral medulla, and some of them showed TH-like immunoreactivity. Sizes of the cell bodies of the lateral horn neurons in C8-T1 segment were significantly increased in 4-wk tail-suspended rats (P<0.05) as compared with that in controls. The results suggest that the neurons in MVZ and the spinal lateral horn may be involved in the adaptation of central cardiovascular regulation during weightlessness.

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats.

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?

Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors.

We investigated the role of caffeine-sensitive intracellular stores in regulating intracellular calcium ([Ca(2+)](i)) and glutamatergic synaptic transmission from rod photoreceptors. Caffeine transiently elevated and then markedly depressed [Ca(2+)](i) to below prestimulus levels in rod inner segments and synaptic terminals. Concomitant with the depression was a reduction of glutamate release and a hyperpolarization of horizontal cells, neurons postsynaptic to rods. Caffeine did not affect the rods' membrane potentials indicating that caffeine likely acted via some mechanism(s) other than a voltage-dependent deactivation of the calcium channels. Most of caffeine's depressive action on [Ca(2+)](i), on glutamate release, and on I(Ca) in rods can be attributed to calcium release from stores: (1) caffeine's actions on [Ca(2+)](i) and I(Ca) were reduced by intracellular BAPTA and barium substitution for calcium, (2) other nonxanthine store-releasing compounds, such as thymol and chlorocresol, also depressed [Ca(2+)](i), and (3) the magnitude of [Ca(2+)](i) depression depended on basal [Ca(2+)](i) before caffeine. We propose that caffeine-released calcium reduces I(Ca) in rods by an as yet unidentified intracellular signaling mechanism. To account for the depression of [Ca(2+)](i) below rest levels and the increased fall rate of [Ca(2+)](i) with higher basal calcium, we also propose that caffeine-evoked calcium release from stores activates a calcium transporter that, via sequestration into stores or extrusion, lowers [Ca(2+)](i) and suppresses glutamate release. The effects of store-released calcium reported here operate at physiological calcium concentrations, supporting a role in regulating synaptic signaling in vivo.

[Echocardiographic assessment of left ventricular structure and function after simulated weightlessness in rats].

Objective. To investigate whether the changes in rat after simulated weightlessness are similar to those in astronaut after flight. Methods. The effects of 4 wk tail-suspension on left ventricular structure and function in rats were examined by echocardiography. Results. After 4 wk of simulated weightlessness, the thickness of both the anterior and posterior wall in left ventricle (LV) showed a general trend of decrease, but these changes were not statistically significant; the end-systolic and end-diastolic internal dimensions (ESD and EDD respectively) of LV decreased significantly; and the end-systolic volume, end-diastolic volume and stroke volume (ESV, EDV and SV respectively) were all reduced; so did the relevant indices of them. There were no significant differences in ejection fraction (EF) and fractional shortening (FS) between the tail-suspended and control groups. The left ventricular mass (LVM) and its index (LVMI) were decreased. The peak velocities of blood flow of aorta, pulmonary artery and mitral valve didn't show any significant change after simulated weightlessness. Conclusion. Medium-term simulated weightlessness may lead to a significant decrease in left ventricular internal dimension, ventricular volume, and mass, and a trend of decrease in mean left ventricular wall thickness. These changes in rats are similar to those observed in astronauts postflight.

Involvement of presynaptic and postsynaptic mechanisms in a cellular analog of classical conditioning at Aplysia sensory-motor neuron synapses in isolated cell culture.

Temporal pairing of presynaptic activity and serotonin produces enhanced facilitation at Aplysia sensory-motor neuron synapses (pairing-specific facilitation), which may contribute to classical conditioning of the gill and siphon withdrawal reflex. This cellular analog of conditioning is thought to involve Ca2+ priming of the cAMP pathway in the sensory neurons. Consistent with that idea, we have found that pairing-specific facilitation by serotonin is greatly reduced by presynaptic injection of a slow Ca2+ chelator or a specific inhibitor of cAMP-dependent protein kinase and is accompanied by a transient increase in the frequency but by no change in the amplitude of spontaneous, miniature EPSPs. However, like post-tetanic potentiation (PTP) and long-term potentiation (LTP) at these synapses, pairing-specific facilitation is also greatly reduced by postsynaptic injection of a rapid Ca2+ chelator or by postsynaptic hyperpolarization during training, although postsynaptic hyperpolarization has no effect on the increase in frequency or on the amplitude of spontaneous EPSPs. These results suggest that pairing-specific facilitation by serotonin involves Hebbian postsynaptic as well as non-Hebbian presynaptic components that interact in some way, perhaps via retrograde signaling, to specifically enhance evoked, synchronized release of transmitter.

Involvement of pre- and postsynaptic mechanisms in posttetanic potentiation at Aplysia synapses.

Posttetanic potentiation (PTP) is a common form of short-term synaptic plasticity that is generally thought to be entirely presynaptic. Consistent with that idea, PTP of evoked excitatory postsynaptic potentials at Aplysia sensory-motor neuron synapses in cell culture was reduced by presynaptic injection of a slow calcium chelator and was accompanied by an increase in the frequency but not the amplitude of spontaneous excitatory postsynaptic potentials. However, PTP was also reduced by postsynaptic injection of a rapid calcium chelator or postsynaptic hyperpolarization. Thus, PTP at these synapses is likely to involve a postsynaptic induction mechanism in addition to the known presynaptic mechanisms.

Nerve activity-dependent variations in clearance of released noradrenaline: regulatory roles for sympathetic neuromuscular transmission in rat tail artery.

The aim of this study was to find out if clearance of noradrenaline released from sympathetic nerve terminals in rat isolated tail artery is a physiological variable and if so, to determine its role for the noradrenaline-mediated neurogenic contraction. The per pulse release of noradrenaline induced by electrical nerve stimulation and the fluctuations of the level of noradrenaline at the receptors driving the contractions were assessed from the electrochemically determined noradrenaline oxidation current at a carbon fibre electrode at the surface of the artery. Both were compared with the noradrenaline-mediated neurogenic contraction. The effects on these parameters of cocaine or desipramine, or of corticosterone, were used to assess the relative roles of neuronal and extraneuronal uptake, respectively. The effects of cocaine or desipramine, which enhance the noradrenaline level at the receptors by blocking neuronal reuptake, were compared with those of yohimbine, presumed to act exclusively by enhancing the per pulse release of noradrenaline. The results seem to support the following tentative conclusions. Clearance of released noradrenaline occurs by neuronal uptake and diffusion, while extraneuronal uptake is negligible. The noradrenaline-induced neurogenic contraction is mediated via adrenoceptors on cells near the plane of the nerve plexus; the excitation spreads from these cells throughout the syncytium. The contractile response to exogenous noradrenaline may also be mediated via receptors on the innervated key cells. Reuptake of noradrenaline into the releasing varicosities, i.e. in "active junctions", is highly efficient for single quanta but rapidly saturated by repeated release, while reuptake of noradrenaline in the "surround" of active junctions is probably rarely saturated and more independent of nerve activity. Saturation of the transporter by repeated release of quanta from the same varicosity and the consequent accumulation of "residual" noradrenaline and increased diffusion out of the junction and recruitment of noradrenaline receptors in the surround may be the cause of the rapid growth of the contraction during a high frequency train. Diffusion of released noradrenaline away from the postjunctional receptors is restricted by a local nerve activity-dependent buffering mechanism which, in spite of fading of the per pulse release, helps maintain the noradrenaline concentration at the receptors and the contraction during long high-frequency trains. Reactivation of the clearance mechanisms upon cessation of nerve activity accelerates the relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)

Spatiotemporal pattern of quantal release of ATP and noradrenaline from sympathetic nerves: consequences for neuromuscular transmission.

The recent explosive development in research concerning the fundamental mechanisms of synaptic transmission helps put the present paper in context. It is now evident that not all transmitter vesicles in a nerve terminal, not even all those docked at its active zones, are immediately available for release (36). We watch, fascinated, the unraveling of the amazingly complex cellular mechanisms and molecular machinery that determine whether or not a vesicle is "exocytosis-competent" (77,78,39,79). Studies on quantal release in different systems show that neurons are fundamentally similar in one respect: that transmitter release from individual active zones is monoquantal (2). But they also show that active zones in different neurons differ drastically in the probability of monoquantal release and in the number of quanta immediately available for release (3). This implies that one should not extrapolate directly from transmitter release in one set of presynaptic terminals (e.g., in neuromuscular endplate or squid giant synapse) to that in other nerve terminals, especially if they have a very different morphology. As shown here, one should not even extrapolate from transmitter release in sympathetic nerves in one tissue (e.g., rat tail artery) to that in other tissues or species (e.g., mouse vas deferens). It is noteworthy that most studies of quantal release are based on electrophysiological analysis and therefore deal with release of fast, ionotropic transmitters from small synaptic vesicles at the active zones, especially in neurons in which these events may be examined with high resolution (49,48,46,33,32). Such data are useful as general models of the release of both fast and slow transmitters from small synaptic vesicles at active zones in other systems, provided that these transmitters are released in parallel, as are apparently ATP and NA in sympathetic nerves. They tell us little or nothing, however, about the release of transmitters (e.g., neuropeptides) from the large vesicles, nor about the spatiotemporal pattern of monoquantal release from small synaptic vesicles in the many neurons that have boutons-en-passent terminals. They show that the time course of effector responses to fast, rapidly inactivated transmitters such as ACh or ATP is necessarily release related. But they do not even address the possibility that the effector responses to slow transmitters such as NA, co-released from the same terminals, may obey completely different rules and perhaps rather be clearance related (7).(ABSTRACT TRUNCATED AT 400 WORDS)

Kinetics of ATP- and noradrenaline-mediated sympathetic neuromuscular transmission in rat tail artery.

Electrophysiological, electrochemical and mechanical recordings were employed to study the kinetics of the release and clearance of adenosine 5'-triphosphate (ATP) and noradrenaline (NA) as sympathetic co-transmitters and of the neurogenic and non-neurogenic contractions in rat isolated tail artery. The life-time of ATP and NA released by a single pulse or 10 pulses at 50 Hz was brief (< 100 ms, or < 3 s, respectively); the neurogenic contractile responses occurred largely after the transmitters had been removed from the extracellular space. The ATP-induced neurogenic contractile responses to a single pulse or 10 pulses at 50 Hz were similar in time-course to the responses to direct muscle stimulation at low voltage; both seemed to be caused by activation of nifedipine-sensitive voltage-gated L-type Ca2+ channels. The alpha 1- and alpha 2-adrenoceptor-mediated components of the NA-induced neurogenic contractile response to 10 pulses at 50 Hz were more delayed and prolonged and determined by properties of the post-receptor mechanisms. The per pulse release of both ATP and NA faded rapidly during long high-frequency trains. So did the ATP level at the receptors and the ATP-induced neurogenic contraction. The NA levels and the contractile responses induced via alpha 1- and alpha 2-adrenoceptors were much better maintained during ongoing stimulation at 20 Hz but relaxed rapidly afterwards, suggesting that nerve activity suppressed, and cessation of nerve activity reactivated NA clearance.

Dual contractile effects of ATP released by field stimulation revealed by effects of alpha,beta-methylene ATP and suramin in rat tail artery.

1. The field stimulation-induced release of endogenous ATP and noradrenaline (NA) and contractile response in rat isolated tail artery were examined. The release of ATP was studied by extracellular electrophysiological recording and that of NA by a novel voltammetrical technique. The effects of the P2-purinceptor antagonist, suramin, on these parameters were compared with those of alpha,beta-methylene ATP, a P2X-purinoceptor desensitizing agent. 2. Neither alpha,beta-methylene ATP (10 microM) nor suramin (100-500 microM) had significant effects on the extracellularly recorded nerve terminal action potential but both abolished the ATP-induced excitatory junction current caused by stimulation at 0.1 Hz. Neither agent affected significantly the voltammetrically measured release of NA induced by 10 or 100 pulses at 20 Hz. 3. Combined blockade of both postjunctional alpha 1- and alpha 2-adrenoceptors by prazosin and yohimbine (both 0.1 microM) profoundly depressed the contractile response to 10 pulses at 20 Hz. The small and fast residual contraction in the presence of these agents was abolished by alpha,beta-methylene ATP (10 microM) and inhibited by suramin in a concentration-dependent manner (10-500 microM; IC50 75 microM) and was hence probably caused by ATP or a related nucleotide. 4. When added first, alpha,beta-methylene ATP (10 microM) or suramin (100-500 microM) delayed the onset and enhanced the amplitude of the neurogenic contraction. This enhanced response was abolished by further addition of prazosin and yohimbine (both 0.1 microM). 5. The K+ channel blocker, tetraethylammonium (10 mM), dramatically enhanced the contractile response to 100 pulses at 1 Hz and caused it to become diphasic. Addition of alpha,beta-methylene ATP (10 microM)or suramin (100-500 microM) abolished the large initial twitch component of this contraction and depressed the tonic phase.6. Like alpha,beta-methylene ATP, suramin (500 microM) had no effect on the contraction caused by exogenous NA (1O nM-l10 microM) or KCI (60 mM); both agents almost abolished the contraction caused by ATP(100 microM).7. In conclusion, (i) the contractile response of rat tail artery to electrical field stimulation is mediated by both ATP and NA, and is thus an expression of ATP-NA co-transmission, (ii) the released ATP exerts two opposite effects via 'P2x-like' purinoceptors, triggering the initial rapid phase of the neurogenic contraction and restricting the NA-mediated component of the contraction; and (iii) the source and possible physiological role of the ATP which causes the inhibitory effect are unknown at present.

Frequency- and train length-dependent variation in the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the field stimulation-induced neurogenic contraction of rat tail artery.

The present paper examines the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the noradrenaline (NA)-induced neurogenic contractile response to field stimulation mainly with 1-100 pulses at 2 or 20 Hz, in the tail artery of adult normotensive rats. Pharmacological tools were employed to isolate and characterize the alpha 1- and alpha 2-adrenoceptor-mediated components of this response. The degree to which the drugs influenced NA release or reuptake was assessed by their effects on the electrochemically determined, stimulation-induced rise in the NA concentration at the innervated outer surface of the media. This response was unaffected by alpha,beta-methylene ATP (10 microM) or suramin (500 microM), added to desensitize or block P2-purinoceptors, respectively prazosin (0.1 microM) or SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxyl]-3-methyl- 1H-2,3,4,5-tetrohydro-3-benzazepine, 0.1 microM), used to block postjunctional alpha 1- and alpha 2-adrenoceptors respectively, nifedipine (10 microM), blocker of Ca2+ influx through L-type channels, and ryanodine (10 microM), which blocks mobilization of Ca2+ from intracellular stores; it was moderately enhanced by yohimbine (0.1 microM), blocker of pre- and postjunctional alpha 2-adrenoceptors, and strongly enhanced by cocaine (3 microM) or desipramine (1 microM), blockers of NA reuptake. Judging from their inhibitory effects on the contractile responses to the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and xylazine, prazosin (0.1 microM) and SK&F 104078 (0.1 microM) could be used to selectively block alpha 1- and alpha 2-adrenoceptors respectively, while yohimbine (0.1 microM) was less selective, strongly depressing alpha 2- and slightly depressing alpha 1-adrenoceptor-mediated responses. The alpha 1-adrenoceptor-mediated component of the contractile response to short trains at 20 Hz was fast in onset, brief in duration and abolished by ryanodine; that mediated by alpha 2-adrenoceptors was more delayed, prolonged and insensitive to ryanodine. Both components were dose-dependently depressed by nifedipine (0.1-10 microM). The small contractile responses to single pulses, or up to 50 pulses at 2 Hz, or short train (< 4 pulses) at 20 Hz, were more markedly depressed by 0.1 microM yohimbine or SK&F 104078 than by 0.1 microM prazosin and, hence, mediated mainly by alpha 2-adrenoceptors. The reverse was true of the much larger response to longer trains at 20 Hz, which thus probably was mediated mainly by alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Fast and local electrochemical monitoring of noradrenaline release from sympathetic terminals in isolated rat tail artery.

Noradrenaline release from sympathetic nerve terminals was evoked by electrical nerve stimulation of an isolated segment of rat tail artery. This release was recorded by a carbon fiber electrode combined with differential pulse amperometry. The active part of the electrode (one carbon fiber 8 microns in diameter and 50 microns in length) was placed in close contact with the arterial surface. The oxidation current appearing at +120 mV and corresponding to the local noradrenaline concentration at the electrode surface was recorded every 0.5 s. No oxidation current was detected under resting conditions, but electrical stimulation evoked an immediate increase in this current. This response was suppressed when tetrodotoxin was added to the perfusion medium and was enhanced when noradrenaline reuptake was inhibited by cocaine. The amplitude of the response was increased with increasing stimulation frequencies (2-25 Hz) and train lengths (1-16 pulses). Finally, the time resolution of the method (0.5 s) was good enough to show that noradrenaline release precedes the postsynaptic response, i.e., the electrically evoked contraction of the artery.

Sympathetic neuromuscular transmission in rat tail artery: a study based on electrochemical, electrophysiological and mechanical recording.

The main purpose of the present thesis was to study sympathetic neuromuscular transmission at the varicosity level, in proximal regions of the isolated tail artery of 'adult' normotensive rat. The strategy was to compare the release and extracellular life-times of ATP and NA, as revealed by electrophysiological and electrochemical methods, respectively, with the contractile response to electrical field stimulation with a single pulse up to 20 min of stimulation at 20 Hz. The extracellularly recorded excitatory junction current (EJC) resolved, based on evidence in the literature, the quantal pulse-by-pulse release of ATP. The electrochemical signal, which reflected the rise and fall in the NA concentration at the surface of the carbon fibre electrode following nerve stimulation (termed delta[NA]CF), monitored on-line and 'in real time', the changes in the NA concentration at the surface of the artery. The total duration of the evoked EJC and delta[NA]CF responses indicated that the life-time of the ATP and NA released by a single pulse, or by short trains (10 pulses) at 50 Hz, was less than 100 ms or 3 sec, respectively. The corresponding contractile responses were mediated by both ATP (or a related nucleotide) and NA (but probably not NPY) via postjunctional P2x-purinoceptors, alpha 1- and alpha 2-adrenoceptors, respectively, and occurred with long delays during which the released ATP and NA had been virtually eliminated or removed from the respective receptors. The kinetics of these contractile responses are thus not determined by the duration of the presence of transmitters at the postjunctional receptors driving the contractions but by post-receptor mechanisms. The large differences in the time-course of these three components of the neurogenic contraction and the interaction between them reveal a novel, kinetic aspect of NA-ATP co-transmission. The relative contribution of NA and ATP to the neurogenic contraction and the relative role of components mediated via alpha 1- and alpha 2-adrenoceptors varied with the length and frequency of the stimulus trains. The ATP-mediated component of this response was always fast and normally small but could be powerful under certain conditions (e.g. in 'young' rats, or in the presence of K(+)-channel blocker). In addition, the results suggest that ATP released by field stimulation restricted both components of the NA-induced neurogenic contraction. The source(s) of the ATP exerting this inhibitory effect and the mechanisms of the inhibition are not clear at present.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrochemical and electrophysiological analysis of the effects of SK&F 104078 on prejunctional alpha 2-adrenoceptors.

SK&F 104078 is proposed to be a selective postjunctional alpha 2-adrenoceptor antagonist. We examined its effects on the electrically evoked release of endogenous noradrenaline (NA) from the rat tail artery and of ATP from the mouse vas deferens, as determined electrochemically or by extracellular recording, respectively. The alpha 2-adrenoceptor antagonist yohimbine (0.1 and 1 microM) increased NA release at both 2 and 20 Hz; the effect of yohimbine was further enhanced by the NA uptake blocker cocaine. SK&F 104078 (0.01-1 microM) did not change NA release at 2 or 20 Hz in the absence or presence of cocaine. NA release at 2 Hz was dose dependently depressed by the alpha 2-adrenoceptor agonist xylazine, an effect reversed by yohimbine (1 microM) but unaffected by SK&F 104078 (0.1 and 1 microM). Similarly, the inhibitory effect of xylazine on ATP release at 0.1 Hz was not influenced by SK&F 104078 (1 microM) but partially reversed by yohimbine (1 microM). The results show (i) that prejunctional alpha 2-adrenoceptors mediate autoinhibition of the release of endogenous NA and ATP from sympathetic nerves in the rat tail artery and in the mouse vas deferens, respectively, and (ii) that SK&F 104078 does not block these receptors in the concentration range 0.01-1 microM.

Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers.

Prior immunologic experience with homologous and heterologous serotype Salmonella strains potentiated the subsequent antibody response when the same strains were used as vaccine carriers of foreign antigens. This potentiation was positively correlated with the appearance of antibody directed against the lipopolysaccharide of the carrier strain. Both serum and mucosal antibody responses against the foreign antigen increased over time. Antibody responses in sera of animals primed with either the homologous or heterologous serotype strain were not statistically significantly different, while animals primed with the homologous serotype strain developed significantly better mucosal antibody responses against the foreign antigen.

K+ and Ca2+ channel blockers may enhance or depress sympathetic transmitter release via a Ca(2+)-dependent mechanism "upstream" of the release site.

Extracellular recording of the pre- and postjunctional electrical activity in guinea-pig or mouse vas deferens or rat tail artery was employed to study the mechanisms by which the K+ channel blockers, tetraethylammonium and 4-aminopyridine and the Ca2+ channel blockers, Cd2+, Mn2+ or nifedipine influence the nerve stimulation-induced release of adenosine 5'-triphosphate as a sympathetic co-transmitter. The K+ and Ca2+ channel blocking agents examined had no effect on the spontaneous quantal release of adenosine 5'-triphosphate. However, addition of tetraethylammonium and 4-aminopyridine inside the recording electrode broadened the nerve terminal action potential and caused it to become more resistant to local application of tetrodotoxin, and dramatically increased the magnitude and tetrodotoxin resistance of adenosine 5'-triphosphate release within the patch. Surprisingly, tetraethylammonium and 4-aminopyridine were equally effective when added outside the recording electrode; now they did not increase the duration of the nerve terminal action potential inside the patch but increased its resistance to locally applied tetrodotoxin and dramatically increased the magnitude as well as the tetrodotoxin resistance of adenosine 5'-triphosphate release from sites inside the patch. Both tetraethylammonium and 4-aminopyridine contributed to these effects, with a strong potentiating interaction. Nifedipine was without effect, but application of 1-100 microM Cd2+ or 1-5 mM Mn2+ either inside or outside the recording electrode blocked adenosine 5'-triphosphate release inside the patch. The results indicate: (i) that the nerve terminal action potential is generated by activation of voltage-gated, regenerative Na+ channels but also has a small component carried by influx of Ca2+ and that it is "normally" terminated by activation of voltage- as well as Ca(2+)-dependent K+ channels; (ii) that the release probability is tonically depressed by the resting K+ efflux, and promoted by the resting Ca2+ influx, "upstream" of the release sites; and (iii) that the upstream control of the release probability may involve both changes in properties of ionic channels in the nerve terminal membrane, and effects on the cytoskeleton leading to changes in the availability of releasable quanta in varicosities within the patch.