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R B Meeker

Publications and source records attributed to R B Meeker.

9 recordsLinked to original sources

Ultrastructural distribution of glutamate immunoreactivity within neurosecretory endings and pituicytes of the rat neurohypophysis.

An ultrastructural analysis of post-embedding glutamate immunocytochemistry within the neural lobe of the pituitary was used to explore the possible role of glutamate within the magnocellular neuroendocrine cells. Relative densities of a colloidal gold marker associated with various cellular and subcellular compartments of the neural lobe were quantified by computer analysis of electron micrographs. Robust glutamate immunoreactivity was observed in both pituicytes (cytoplasm, mitochondria and nucleus) and neurosecretory endings. Within the neurosecretory endings, glutamate staining was specifically localized to the microvesicles with no overlap into the neurosecretory granule population. Stimulation of the vasopressin/oxytocin neurosecretory system by water deprivation increased glutamate content in pituicytes and mitochondria within neurosecretory endings but had little influence on microvesicle glutamate content. The results are consistent with the existence of multiple functional pools of immunoreactive glutamate in both pituicytes and neurosecretory endings. Microvesicles within the neurosecretory endings exhibit many properties of secretory vesicles, appear to be functionally independent of the neurosecretory granules, and have sufficient glutamate immunoreactivity to suggest that this amino acid may be compartmentalized for release in the neural lobe.

Animals

Amygdala kindling elevates plasma vasopressin.

Acute and chronic effects of epilepsy on endocrine function are known to occur in humans with partial seizures of limbic origin and in animals with limbic kindled seizures. The amygdala, a component of the limbic system, has dense hypothalamic connections and amygdala stimulation in monkeys and cats result in vasopressin release. In the present study we sought to determine if amygdala stimulation in the rats results in an immediate acute release of vasopressin and to determine if acute or chronic changes occur in vasopressin release in the fully kindled animal. Plasma vasopressin, osmolality and hematocrit were measured in blood samples drawn from rats with implanted venous catheters before and after stimulation and at different stages of kindling. Low-frequency (15 Hz) electrical stimulation of the amygdala was followed by an immediate, 3-fold increase in plasma vasopressin concentration. Moreover, although the 60 Hz kindling stimulus did not result in a significant immediate rise in plasma vasopressin prior to kindling, after kindling to stage 5 seizures the 60 Hz kindling stimulus resulted in seizures and a significant immediate rise in plasma vasopressin. In addition, we found that kindling was followed by a significant, though modest, rise in the resting plasma vasopressin without an accompanying change in osmolality or hematocrit. We conclude that kindling results in a persistent alteration in the vasopressinergic neuroendocrine system.

Amygdala

Muscarinic cholinergic control of vasopressin secretion from the acute hypothalamoneurohypophysial explant.

Much of the afferent input thought to modulate vasopressin release from the magnocellular neuroendocrine cells of the supraoptic nucleus terminates in the region dorsal to the supraoptic nucleus. Cholinergic cells within this region may participate in the local processing of these afferent signals via synapses onto muscarinic cholinergic receptors. To investigate the role of these local synapses in vasopressin secretion, we characterized the muscarinic cholinergic influence on vasopressin secretion from the acute hypothalamoneurohypophysial explant in vitro. Acetylcholine induced a small dose-related secretion of vasopressin which could be totally blocked by atropine but not the nicotinic cholinergic antagonist, hexamethonium. Nicotine failed to release vasopressin from the explant, whereas alpha-bungarotoxin elicited a hypothalamic release of vasopressin which was atropine insensitive. Thus, local muscarinic receptors in the hypothalamus appear to participate in the control of neurohypophysial vasopressin secretion. The small magnitude of effect, however, is consistent with an indirect modulatory role rather than a major driving force for activation of the magnocellular neurons.

Acetylcholine

Vasopressin mRNA expression in individual magnocellular neuroendocrine cells of the supraoptic and paraventricular nucleus in response to water deprivation.

Vasopressin neuroendocrine function involves the regulation of both secretion and synthesis from magnocellular neuroendocrine cells but the coordination of these two processes is poorly understood. To explore the temporal relationship between physiological stimulation and vasopressin mRNA levels we measured vasopressin mRNA content within individual magnocellular neurons of the supraoptic and paraventricular nucleus during the course of water deprivation. Analysis of autoradiographic silver grain densities from in situ hybridization of an [125I]dCTP-labeled oligonucleotide specific for vasopressin mRNA revealed a wide variety of resting vasopressin mRNA levels and differential responses to water deprivation in the magnocellular neuroendocrine cells. During water deprivation, the vasopressin mRNA content of the paraventricular nucleus increases rapidly and with shorter latency and greater incremental response than the supraoptic nucleus. Double-labeling experiments with combined in situ hybridization and immunocytochemistry identified a population of vasopressin immunoreactive cells which maintain very low basal levels of vasopressin mRNA. The location of these cells correlates with the location of increased silver grain densities during water deprivation. One subset of vasopressin magnocellular neurons failed to show high levels of vasopressin mRNA, indicating that all cells are not equally responsive to water deprivation. These patterns of vasopressin mRNA expression suggest the presence of functional subpopulations of vasopressin neuroendocrine cells which may reflect stimulus-specific patterns of afferent input to the supraoptic and paraventricular nucleus.

Animals

Vasopressin and oxytocin regulation of cyclic AMP accumulation in rat hypothalamo-neurohypophysial explants in vitro.

Addition of vasopressin to hypothalamo-neurohypophysial explants in vitro increased cyclic AMP accumulation whereas exogenous oxytocin decreased cyclic AMP. An opposite response pattern was observed in the neural lobe of the pituitary where vasopressin decreased and oxytocin increased cyclic AMP accumulation. Forskolin elicited a 3-fold greater increase in cyclic AMP in the neural lobe than in the supraoptic nucleus and enhanced the sensitivity of the tissues to both vasopressin and oxytocin. The ability of both vasopressin and oxytocin to modulate local cyclic AMP metabolism suggests the possibility of internal feedback within the hypothalamo-neurohypophysial system.

Acetylcholine

GABA-mediated behavioral inhibition during ontogeny in the mouse.

Although immature rats and mice generally demonstrate poor behavioral inhibitory capacities, some recent evidence may indicate the presence of substantial inhibitory control. The present experiment investigated the possibility that gamma-aminobutyric acid (GABA) systems may mediate some behavioral inhibition during early development. Mice 9-100 days old were injected with the GABA-elevating agent amino-oxyacetic acid (AOAA) and tested for behavioral activity. High levels of locomotor activity characteristic of immature control mice were attenuated following AOAA injection, whereas AOAA had little effect on the activity of adult mice. Moreover, AOAA produced a period of rebound hyperactivity for young but not for adult mice. These findings suggest that although GABA systems may mediate early behavioral inhibition, coordination between excitatory and inhibitory capacities matures slowly. In a second experiment the dopamine-beta-hydroxylase inhibitor FLA-63 prevented rebound hyperactivity in young mice pretreated with AOAA, suggesting that the excitatory component may be mediated by noradrenergic systems.

Aminooxyacetic Acid

(-)-Hydroxycitrate and conditioned aversions.

The capacity of various salts of (-)-hydroxycitrate to produce conditioned rejection of a 0.25% saccharin solution was evaluated. The ethylenediamine salt of (-)-hydroxycitrate produced strong conditioned rejection of saccharin under both deprivation and nondeprivation conditions, but this effect was less than produced by equimolar doses of lithium chloride. The sodium salt of hydroxycitrate produced no conditioned rejection of saccharin in water deprived rats but did so in nondeprived animals. In these experiments, food intake was reduced by (-)-hydroxycitrate only during the first hour following administration of the drug. The magnitude of appetite rejection did not correspond to the degree of conditioned rejection, lending support to the conclusion that the food intake reduction was not merely a consequence of aversive effects of the drug.

Animals

Effects of alpha-MSH on motivation, vigilance and brain respiration.

In a series of experiments designed to assess the effects of alpha-MSH on various motivational processes, it was observed that the hormone can slightly decrease food intake and increase water consumption during the first hr after administration in rats. alpha-MSH also modified avoidance behavior in 1- and 3-day-old chicks, but there were no reliable effects on activity, distress vocalizations and the tonic immobility response. alpha-MSH appeared to modulate the sleep-waking activity of rats, and the most prominent effect was an increase of slow wave sleep during the 2-3 rd hr after treatment. A possible second effect was a homogenization of sleep patterns--with poor sleepers exhibiting increases of activated sleep and good sleepers a reduction. Measurement of in vitro brain oxygen consumption indicated that mice treated with alpha-MSH exhibit an 18% reduction in respiration of the brain stem section which includes the locus coeruleus, but did not reliably change respiration in forebrain cortices. alpha-MSH also produced a modest 14% increase of plasma glucose. These results are discussed in terms of possible modulation by alpha-MSH of activity in central autonomic cell groups such as the locus coeruleus.

Animals