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Biomedical subjects

S A Joseph

Publications and source records attributed to S A Joseph.

At least 55 records · Page 3Linked to original sources

The effects of nitrous oxide on the secretory activity of pro-opiomelanocortin peptides from basal hypothalamic cells attached to cytodex beads in a superfusion in vitro system.

Dispersed cells from adult rat basal hypothalami, attached to Cytodex-3 microcarrier beads, were placed in a column and superfused with aerated high glucose media or media enriched with variable concentrations of nitrous oxide with oxygen. beta-Endorphin and alpha-MSH content was measured in the effluent collected during superfusion and demonstrated a near constant baseline release. Nitrous oxide, 60% (P less than 0.025) and 80% (P less than 0.02), caused significant increases in release of beta-endorphin. Potassium chloride (50 mM) caused a significant increase in release (P less than 0.007) of beta-endorphin whereas saline and 30% nitrous oxide did not. Neither nitrous oxide-enriched media nor potassium chloride had any statistically significant effect on alpha-MSH release. The increase in beta-endorphin secretory activity during exposure to nitrous oxide demonstrates that nitrous oxide may have a stimulatory effect on central pro-opiomelanocortin neurons.

Animals↗

Effects of naloxone on breathing movements during hypercapnia in the fetal lamb.

To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements.

Animals↗

Central beta-endorphin release and recovery after exposure to nitrous oxide in rats.

To explore the hypothesis that nitrous oxide stimulates the beta-endorphin system in vivo, rats were exposed to nitrous oxide/oxygen at variable concentrations for one hour. beta-Endorphin concentration at sites along the neuraxis functionally involved with analgesia was elevated in nitrous oxide-exposed animals. The increase in beta-endorphin concentration was statistically significant at nitrous oxide concentrations of 60 and 80%. This elevation of beta-endorphin levels depended on the concentration of nitrous oxide delivered rather than on the duration of exposure. With cessation of nitrous oxide anesthesia, beta-endorphin concentration returned to control levels within 30 minutes.

Animals↗

Anatomy of the corticotropin-releasing factor and opiomelanocortin systems of the brain.

Using antiserums generated against the neuropeptides corticotropin-releasing factor (CRF), beta-endorphin, and adrenocorticotropin, we have immunocytochemically mapped the organization of these hormones throughout the brain. The distribution of CRF perikarya is widespread throughout the forebrain, brain stem, and spinal cord. The central opiomelanocortin system is represented by two separate pools of neuronal perikarya: the hypothalamic arcuate pool, and the medullary (nucleus tractus solitarius) pool. From these groups fibers distribute widely throughout forebrain and brain stem. A conspicuous codistribution pattern exists between the CRF perikarya and opiomelanocortin fibers. Analysis of these systems within the brain stem and spinal cord reveals innervation and distribution patterns within regions containing catecholamine systems, areas associated with regulation of sympathetic and parasympathetic outflow, cardiovascular and respiratory homeostatic centers, and regions associated with stress, autonomic homeostasis, and pain modulation. By virtue of these extensive brain-stem distributions, it is suggested that an anatomical substrate exists for participation of these peptide systems in the integration of certain autonomic, visceral, and homeostatic mechanisms.

Adrenocorticotropic Hormone↗

Pulmonary platelet trapping induced by beta-endorphin injection in the cerebrospinal fluid in dogs.

The effect of beta-endorphin injected into either the lateral ventricle or the cisterna magna on blood pressure, heart rate, peripheral platelet and leukocyte counts, hematocrit levels, catecholamines, and pulmonary platelet trapping was studied. The effect of endotoxin on the endogenous opiocortin system was also investigated. Injection of beta-endorphin caused a significant decrease in blood pressure, bradycardia, and pulmonary platelet trapping. beta-Endorphin had no effect on peripheral platelet and leukocyte counts, catecholamines, or hematocrit levels. Endotoxin shock caused a marked rise in circulating beta-endorphin and a decrease in cerebrospinal fluid beta-endorphin. Our results confirm that endotoxin shock activates the opiocortin system, and we suggest that the endorphins may participate in the evolution of the lung injury seen in septic shock.

Animals↗

Co-localization of CRF-ir perikarya and ACTH-ir fibers in rat brain.

The distribution of corticotropin-releasing factor immunoreactive (CRF-ir) perikarya and ACTH-ir fibers was examined immunocytochemically, in adjacent sections, in the forebrain and brainstem of the rat. Throughout the nervous system, a remarkable concordance of localization of these neuropeptide systems was noted. Both ACTH-ir fibers and CRF-ir perikarya were conjointly distributed within discrete hypothalamic, limbic and brainstem/autonomic regions previously demonstrated to contain opiate receptors and opiocortin (beta-endorphin, beta-LPH, ACTH) fibers. In view of the demonstrated interactions of CRF with the peripheral (pituitary) opiocortin system, these data suggest the possibility of a similar relationship of CRF and opiocortin systems in the central nervous system as well.

Adrenocorticotropic Hormone↗

Immunocytochemical localization of ACTH1-39 in the brainstem of the rat.

The immunocytochemical distribution of ACTH1-39 (adrenocorticotropin hormone), a member of the opiocortin family of peptides, was examined in the brainstem of the rat. Immunoreactive ACTH fibers were localized in many serotonin-containing raphe nuclei and in the norepinephrine- and dopamine-containing regions throughout the brainstem. Brainstem areas involved in pain mediation contained immunoreactive ACTH fibers as well as several cranial nerve nuclei and nuclei associated with cardiovascular and respiratory functions.

Adrenocorticotropic Hormone↗

Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system.

Immunocytochemical localization of ACTH-opiocortin perikarya was demonstrated in the medulla of colchicine-treated rat. Neuronal cell bodies and fibers containing ACTH-immunoreactivity were abundant in the caudal region of the nucleus tractus solitarius, specifically within pars commisuralis. Location of these opiocortin neurons within the nucleus tractus solitarius provides additional evidence for a role of these peptides in cardiovascular functions.

Adrenocorticotropic Hormone↗

Corticotropin releasing factor: immunocytochemical localization in rat brain.

Using antiserum generated against the synthetic CRF1-41 we have immunocytochemically localized perikarya and processes in rat brain. Areas observed to have particularly dense accumulation of CRF-ir cells were in the extra-hypothalamic areas of nucleus accumbens septi, nucleus of the stria terminalis, the medial preoptic region, and the central amygdaloid nucleus. Within the hypothalamus cell bodies were scattered throughout the anterior hypothalamic region and densely packed in the paraventricular nucleus. Fibers appear most dense in the lateral septal region and throughout the external layer of the median eminence.

Afferent Pathways↗

Relationship of the central ACTH-immunoreactive opiocortin system to the supraoptic and paraventricular nuclei of the hypothalamus of the rat.

ACTH-immunoreactive (ir) fibers of the central opiocortin system are present in high density in the mid-portion of the paraventricular nucleus (PVN). ACTH-ir fibers, however, do not appear to directly contact oxytocin-ir vasopressin-ir, containing perikarya or axons of vasopressinergic neurons. Magnocellular neurons located more anteriorly and posteriorly in the PVN as well as those located laterally have few ACTH-ir fibers associated with them. No ACTH-ir fibers are present in the supraoptic nucleus.

Adrenocorticotropic Hormone↗

The distribution of enkephalin in the mediobasal hypothalamus of the mouse brain: effects of neonatal administration of MSG.

The immunocytochemical distribution of the pentapeptides, methionine- and leucine-enkephalin (Enk) were examined in the mediobasal hypothalamus of control mice with a neurotoxic lesion of the arcuate nucleus due to neonatal treatment of monosodium glutamate (MSG). In control mice immunoreactive Enk cells and fibers were present in the arcuate nucleus. Enk fibers were found in the subependymal, internal and external layers of the median eminence. At 60 days of age, mice receiving neonatal injections of MSG displayed symptoms of neuroendocrine deficiencies. Histochemical methods revealed a loss of Enk immunoreactivity from the arcuate nucleus and all layers of the median eminence. These results suggest that the lack of Enk cells and fibers in the mediobasal hypothalamus of MSG-treated animals is partially responsible for the endocrine dysfunctions exhibited by these animals.

Animals↗

Distribution of somatostatin in the mouse brain: effects of neonatal MSG treatment.

Immunocytochemical analysis using antisera generated against the brain peptide somatostatin (SRIF) was examined in the brain of normal mice and in mice with chemical lesions of the arcuate nucleus produced neonatally by the administration of monosodium glutamate (MSG). In the normal mouse brain, SRIF immunoreactivity was seen in perikarya of the preoptic and hypothalamic periventricular nuclei. The normal distribution of SRIF fibers was apparent in several hypothalamic nuclei including the arcuate nucleus and in the internal and external zones of the median eminence. Extrahypothalamic sites of SRIF immunoreactive neurons and fibers were also observed throughout the telencephalon. At 60 days of age, certain neuroendocrine deficiencies, including growth parameters and obesity, were apparent in MSG-treated newborn mice. Analysis of SRIF projections in the brain of MSG-treated mice demonstrated a neurotoxic effect on arcuate neurons and a loss of SRIF projections to this region as well. Other components of the SRIF system in brain appeared unaffected. SRIF fibers of the arcuate region seem to originate from neuronal perikarya of the periventricular nucleus suggesting that MSG-induced endocrine deficiencies may be due to SRIF interactions at the level of the arcuate nucleus.

Animals↗

The distribution and cells of origin of ACTH(1-39)-stained varicosities in the paraventricular and supraoptic nuclei.

ACTH(1-39)-immunoreactive fibers and varicosities were localized using indirect immunofluorescence histochemistry in normal rats, and were found to be distributed in specific parts of the parvocellular division of the paraventricular nucleus, and in regions of the magnocellular division of the paraventricular and supraoptic nuclei in which oxytocinergic cells predominate. A combined retrograde transport-immunohistochemical method was used to confirm that these projections arise from a group of ACTH(1-39)-stained cells in the arcuate nucleus (and in adjacent regions along the base of the hypothalamus), and to describe their distribution within this region.

Adrenocorticotropic Hormone↗

Immunocytochemical distribution of LHRH neurons and processes in the rat: hypothalamic and extrahypothalamic locations.

The distribution of luteinizing hormone-releasing hormone (LHRH)-immunoreactive perikarya and processes was examined, in the untreated rat, with the unlabeled antibody enzyme method of immunocytochemistry on thick 50 micron vibratome sections. LHRH neurons were primarily observed in the preoptico-anterior hypothalamic and septal areas. Projections from these cell bodies to the median eminence form three distinct pathways, one laterally along the course of the optic tracts, one medially through the periventricular stratum of the third ventricle, and one through the tractus infundibularis. In addition, some of these cell bodies project to the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO). LHRH immunoreactive neurons were also noted in the anterior olfactory regions; they project along the medial olfactory tract to the olfactory bulb.

Animals↗

Topography of the ACTH-immunoreactive neurons in the basal hypothalamus of the rat brain.

Cell bodies of the opiocortin neurons were stained immunocytochemically with ACTH antiserum and their location in the basal hypothalamus of the rat brain was mapped. They are present throughout the entire extent of the hypothalamus, from retrochiasmatic area to mammillary body. In the retrochiasmatic area they are a single, midline group horizontally oriented and lying close to the ventral surface. Throughout the extent of the median eminence, ACTH-ir perikarya are located in the arcuate nucleus, adjacent periventricular stratrum and internuclear space between arcuate and ventromedial nuclei; as a group, they are oriented in a dorso-lateral plane. In the mammillary region, the nucleus assumes a more horizontal orientation again, lying close to the ventral surface. No regional differences were noted in cell density except in the retrochiasmatic area and terminal portion of the mammillary region where they were approximately 30% fewer in number.

Adrenocorticotropic Hormone↗

Relationship of the central ACTH-immunoreactive opiocortin system to the median eminence and the pituitary gland of the rat.

By immunocytochemical methods, the present study describes ACTH-immunoreactive fibers in the pituitary stalk and neural lobe. This opiocortin-hypothalamo-neural lobe projection arises in a bed nucleus of perikarya in the basal hypothalamus, follows supraoptico-hypophyseal fibers in the zona interna of the median eminence, and distributes throughout the neural lobe. No ACTH-immunoreactive fibers project to the zona externa; some are present in the subependymal layer and at the lateral margins of the median eminence. Further studies must identify the role of these fibers in posterior lobe function. It remains also to be determined whether this system terminates upon primary pituitary portal capillaries and delivers opiocortin neuropeptides to the adenohypophysis.

Adrenocorticotropic Hormone↗