Challenging the culture of sport and alcohol.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
G Munro
Publications and source records attributed to G Munro.
Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat.
1. We have tested the hypothesis that morphine withdrawal excitation of oxytocin neurones that follows from administration of naloxone to morphine-dependent rats is a consequence of excitation of noradrenergic neurones. 2. Female rats were made morphine dependent by intracerebroventricular (i.c.v.) infusion of the opioid at increasing doses over 5 days. On the sixth day, the rats were anaesthetized with urethane or pentobarbitone and prepared for blood sampling to determine plasma oxytocin by radioimmunoassay or for in vivo extracellular recording of the firing rate of identified oxytocin neurones from the supraoptic nucleus. Morphine withdrawal was induced by intravenous (i.v.) injection of the opioid antagonist naloxone (5 mg kg-1). 3. In one group of rats the noradrenergic projections to the hypothalamus were lesioned by i.c.v. injection of 6-hydroxydopamine immediately prior to the induction of morphine dependence. In these rats the oxytocin secretion induced by i.v. cholecystokinin was reduced to 9 % of that seen in sham-lesioned rats but in contrast, no attenuation of morphine withdrawal-induced oxytocin secretion was observed. 4. i.c.v. infusion of the alpha1-adrenoreceptor antagonist benoxathian, at up to 5.3 microg min-1, dose- dependently inhibited the withdrawal excitation of oxytocin neurones in morphine-dependent rats under urethane anaesthesia, and benoxathian reduced withdrawal-induced oxytocin secretion to 37 % of that of vehicle-infused rats. i.c.v. benoxathian also inhibited the activity of oxytocin neurones in morphine-naïve rats. Similarly, microdialysis administration of 2 mM benoxathian directly onto the surface of the supraoptic nucleus reduced the activity of oxytocin neurones by 53 %. 5. Thus noradrenergic systems are not essential for the expression of morphine withdrawal excitation, since chronic neurotoxic destruction of the noradrenergic inputs to the hypothalamus did not affect the magnitude of withdrawal-induced oxytocin secretion. However, tonically active noradrenergic inputs influence the excitability of oxytocin neurones, and acute antagonism of this noradrenergic tone can powerfully impair the ability of oxytocin neurones to exhibit morphine withdrawal excitation.
Adrenergic alpha-Antagonists↗
Altered cholecystokinin binding site density in the supraoptic nucleus of morphine-tolerant and -dependent rats.
The processes underlying the development of neuronal tolerance to and dependence upon opiates are not yet fully understood. To evaluate a possible role for cholecystokinin (CCK) in these processes, quantitative receptor autoradiography and in situ hybridisation histochemistry were used to study both the density and distribution of sulphated CCK octapeptide (CCK8S) binding sites and preproCCK peptide mRNA levels within the dorsal (oxytocin neurone-rich) supraoptic nuclei of rats given an intracerebroventricular (i.c.v.) infusion of morphine over 5 days, which is known to induce tolerance and dependence in mechanisms regulating oxytocin neurones. Specific CCK8S binding was significantly increased in the supraoptic nuclei of both morphine-dependent and salt-loaded (2% sodium chloride to drink for 48 h) rats compared to their respective controls (P < 0.05). In situ hybridisation histochemistry revealed no difference in preproCCK mRNA levels within supraoptic neurones of (i.c.v.) morphine-treated compared with either i.c.v. vehicle-treated or untreated control animals. These results suggest that CCK receptor mechanisms involved in the control of magnocellular oxytocin neurone activation are upregulated during chronic morphine treatment, and this may favour increased sensitivity to CCK, thereby offsetting the inhibitory actions of morphine, contributing to tolerance and perhaps to the withdrawal excitation characteristic of dependence.
Animals↗
Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats.
We investigated whether release of oxytocin into the supraoptic nucleus is involved in morphine-withdrawal excitation of oxytocin neurones. Retrodialysis of naloxone into the supraoptic nucleus of morphine-dependent rats increased intranuclear oxytocin release by 56.5p +/- 12.7% whereas no change was seen in vehicle-treated dependent rats. In another experiment, in morphine-dependent rats given intravenous (i.v.) naloxone, intracerebroventricular (i.c.v.) oxytocin receptor antagonist injection reduced the increase of plasma oxytocin concentration (to 28-fold) compared with i.c.v. vehicle (62-fold increase). Finally, the increase in oxytocin neurone firing rate following morphine-withdrawal in the presence of i.c.v. oxytocin antagonist infusion was 28% of the steady state firing rate (15-20 min later) and this was lower (p < 0.05) than the percentage increase in i.c.v. vehicle-infused rats (89%). Thus, central endogenous oxytocin may be involved in withdrawal excitation of oxytocin neurones.
Action Potentials↗
Activation of oxytocin neurones by systemic cholecystokinin is unchanged by morphine dependence or withdrawal excitation in the rat.
1. Morphine inhibits supraoptic nucleus oxytocin neurones directly and presynaptically via inhibition of afferent noradrenergic endings. 2. We studied whether morphine tolerance/dependence (induced by intracerebroventricular (I.C.V.) morphine infusion) alters the responsiveness of oxytocin neurones to systemic cholecystokinin (CCK), a stimulus which activates oxytocin neurones via the release of noradrenaline. 3. CCK (20 micrograms kg-1, i.v.) increased plasma oxytocin concentrations similarly in urethane-anaesthetized morphine-naive and -dependent rats. In naive rats, I.C.V. (10 micrograms) and i.v. morphine (0.5 mg kg-1) reduced CCK-induced oxytocin secretion by 95 +/- 4 and 49 +/- 10%, respectively. In dependent rats, i.v. morphine reduced CCK-induced release by only 8 +/- 9%, indicating tolerance. 4. In urethane-anaesthetized rats, i.v. CCK increased the firing rates of oxytocin neurones similarly in morphine-naive and -dependent rats (by 1.2 +/- 0.2 and 1.4 +/- 0.3 spikes s-1 maximum, respectively, over 5 min). Naloxone did not alter spontaneous or CCK-induced activity in naive rats but increased activity in dependent rats (by 3.4 +/- 0.5 spikes s-1), indicative of withdrawal excitation; however, the response to CCK remained unchanged after naloxone. 5. Systemic CCK did not trigger withdrawal, nor did it have a greater excitatory effect in dependent rats. Thus, morphine withdrawal excitation of oxytocin neurones does not involve supersensitivity to the noradrenergic input, or hypersensitivity of this input to i.v. CCK. Tolerance apparently occurs both at the cell bodies of oxytocin neurones in the supraoptic nucleus and in their noradrenergic input. However, dependence is apparent only at the cell bodies.
Afferent Pathways↗
Effect of an immunisation campaign in Natal and KwaZulu on vaccinaton coverage rates, 1990-1991.
In 1990 the Department of National Health and Population Development of South Africa launched a nationwide immunisation campaign targeted mainly at measles. In order to measure the effect of the campaign on vaccination coverage rates for children, pre- and post- campaign vaccination coverage surveys were undertaken using a modified Expanded Programme for Immunisation technique, stratified for race and urban/rural residence. The results in KwaZulu-Natal showed no significant increase in measles vaccination coverage for any race rates after the campaign (as documented by Road-to-Health cards). There was a decrease in coverage of the black population. However, when a history of measles vaccination was accepted, the results showed an increase in coverage. The results call into question the effectiveness of immunisation campaigns as a strategy for raising vaccination coverage levels, as well as their having a sustained impact on the incidence of measles. Alternative strategies, such as the strengthening and expansion of existing primary health care services, should be considered.
Child, Preschool↗
Central endogenous opioid inhibition of supraoptic oxytocin neurons in pregnant rats.
Naloxone increases oxytocin secretion in pregnant rats, suggesting restraint by endogenous opioids but we have previously reported that oxytocin nerve terminals in the neural lobe become desensitized to opioid actions in late pregnancy. Therefore, we sought evidence for opioid inhibition on oxytocin cell bodies and their inputs at this time. In conscious 21 d pregnant rats naloxone increased the number of neurons expressing Fos (an indicator of neuronal activity) in the supraoptic nucleus (SON) but had no effect on 16 d pregnant or virgin rats. Release of oxytocin within the SON, measured by microdialysis in conscious rats, was also increased by naloxone in late pregnancy but not before. Nor-binaltorphimine, a specific kappa- opioid antagonist, did not increase Fos or affect oxytocin release within the SON in any group. In anesthetized rats the firing rate of SON neurons was recorded and oxytocin neurons identified by an excitatory response to intravenous cholecystokinin. Naloxone potentiated the cholecystokinin-induced firing rate response on day 21 of pregnancy but not in 16 d pregnant or virgin rats. Blood sampling in anesthetized rats showed that naloxone also increased the oxytocin secretory response to cholecystokinin in late pregnant rats. We conclude that in late pregnancy, after day 16, endogenous opioids inhibit oxytocin neurons either directly, on their cell bodies, or presynaptically on inputs. These endogenous opioids do not act through kappa- opioid receptors since nor-binaltorphimine was ineffective, but may act via mu-opioid receptors. Thus, the opioids restrain premature oxytocin secretion until parturition when there is a high demand for it.
Animals↗
Opioids influence neurohypophysial but not central oxytocin release following direct hyperosmotic stimulation of the supraoptic nucleus in urethane-anaesthetised rats.
Microdialysis was used to apply an osmotic stimulus (0.5 M NaCl-aCSF) into both supraoptic nuclei (SON) to investigate the role of endogenous opioid peptides in the control of both central and peripheral oxytocin release in response to this stimulus. There were no differences in central peptide release during direct hyperosmotic stimulation between groups of rats given either vehicle, morphine (5 mg/kg) or naloxone (5 mg/kg) intravenously. Naloxone potentiated oxytocin release into blood; this suggests that endogenous opioid peptides at the level of the neurohypophysis, but not in the SON are important modulators of oxytocin release to this stimulus. However morphine blocked oxytocin release into blood indicative of a central inhibitory action on the firing rate of oxytocin neurones, contrasted with insensitivity to morphine of oxytocin secretion from the dendrites stimulated directly by hyperosmolarity.
Animals↗
Conservation of the gene encoding streptococcal antigen I/II in oral streptococci.
The spaP gene of Streptococcus mutans serotype c encodes a major cell surface protein, streptococcal antigen (SA) I/II, with an Mr of 185,000, that is thought to be involved in bacterial adhesion to teeth. Proteins with significant amino acid sequence homology to SA I/II have also been found in S. sobrinus and S. sanguis. The objectives of this study were to investigate the conservation of the spaP gene in the mutans groups of streptococci and to determine whether homologous genes were present in other species of alpha-hemolytic streptococci. DNA extracted from representative strains of 19 streptococcal species was examined by Southern hybridization and partial DNA sequence analysis. A series of five overlapping DNA probes from the spaP gene were amplified by the polymerase chain reaction and used in the Southern hybridizations. The entire gene was found to be well conserved in all strains of S. mutans serotypes c, e, and f investigated. A probe from the 3' region of the gene, which encodes residues 857 to 1207 of the SA I/II protein, hybridized with DNA from a number of mutans streptococci, as well as with DNA from nonmutans alpha-hemolytic streptococci. Conservation within this region was further demonstrated by sequencing gene fragments of two strains of S. intermedius and S. oralis. The results show that some regions of the spaP gene are highly conserved not only in the mutans group of streptococci but also in other nonmutans alpha-hemolytic streptococci. This suggests that a family of cell surface proteins which, by analogy with the 185,000-Mr SA I/II of S. mutans, could be involved in bacterial adhesion might exist.
Amino Acid Sequence↗
Chromatographic methods for determining the identity, strength and purity of ranitidine hydrochloride both in the drug substance and its dosage forms--an exercise in method selection, development, definition and validation.
The selection, development, definition and validation of selective stability-indicating procedures for high-performance liquid chromatographic and thin-layer chromatographic analyses of ranitidine hydrochloride are described. The procedures used in conjunction can be applied to the quality assurance and stability assessments of both the drug substance and its dosage forms and serve to establish the identity, strength and purity of this drug used in the treatment of peptic ulcer and related conditions.
Chromatography↗
The gas chromatographic analysis of the diastereoisomeric forms present in some phenylalkanolamines [proceedings].
Explore the source record for details and available documents.
Chromatography, Gas↗