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Biomedical subjects

W K Samson

Publications and source records attributed to W K Samson.

At least 109 records · Page 6Linked to original sources

Gastrointestinal hormones: central nervous system localization and sites of neuroendocrine actions.

It was established that VIP (vasoactive intestinal peptide), secretin, CCK (cholecystokinin), gastrin and motilin can be localized to the CNS by immunologic means. Whether or not these immuno-crossreactivities represent peptides identical to those in the g.i. tracts remains to be established. The neuronal localization of these five peptides in the gut predicted, however, their presence in neurons of the CNS. Furthermore, their presence within the hypothalamus and pituitary suggested physiological roles for these hormones in anterior pituitary function. We have now demonstrated the direct actions of VIP, secretin, gastrin and motilin on pituitary hormone release in vitro. Perhaps more importantly, we have described a hypothalamic site of action of VIP, secretin, CCK and gastrin to alter hormone release in vitro. Our data, taken in concert with those of other groups, suggest a modulatory role for the g.i. hormones and indicate the possible symphonic control by many hormones and transmitter candidates of distinct secretory events in the pituitary. Indeed, these data indicate the complexity underlying the finally tuned hypothalamus-pituitary-target tissue axis.

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Vasoactive intestinal peptide stimulates luteinizing hormone-releasing hormone release from median eminence synaptosomes.

Third ventricular injections of vasoactive intestinal polypeptide (VIP) result in increased circulating levels of luteinizing hormone (LH) in conscious, freely moving, ovariectomized (OVX) rats. This effect of VIP has been hypothesized to be mediated via stimulation of luteinizing hormone-releasing hormone (LH-RH) secretion from hypothalamic neurons since VIP is incapable of stimulating LH release from rat pituitaries in vitro. To test this hypothesis, crude synaptosomes were prepared from OVX rat median eminence (ME) tissue. Release of LH-RH from these preparations displayed time and temperature dependencies. Additionally, depolarization-induced (elevated K+) LH-RH release was demonstrated to be Ca2+-dependent. VIP, in doses ranging from 1.5 x 10(-7) to 1.5 x 10(-9) M, was capable of stimulating significantly greater LH-RH release from ME synaptosomes than that from control preparations. VIP's close structural homolog, glucagon, was incapable at the same doses of stimulating increased LH-RH release. These findings offer an explanation for the effect of third ventricularly injected VIP on LH release and suggest a modulatory role for VIP in the hypothalamic control of LH secretion.

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The effect of fever on central alpha-MSH concentrations in the rabbit.

The recent demonstration of the ability of centrally administered alpha-MSH to reduce pyrogen-induced fever in rabbits suggested a role for the peptide in central temperature control. Using a sensitive radioimmunoassay we have established the presence of immunoreactive alpha-MSH (ir alpha-MSH) in discrete CNS sites of the rabbit and have demonstrated a distribution of this activity similar to that seen in other species. Pyrogen-induced fever did not alter concentrations of ir alpha-MSH in tissue extracted from the paraventricular region of the hypothalamus, median eminence, midbrain central grey, preoptic/anterior hypothalamic region, pineal or pituitary. A decrease in arcuate nucleus ir alpha-MSH content was seen in febrile animals, although this change was not statistically significant. Significantly higher levels of ir alpha-MSH were detected in septal extracts of febrile rabbits (0.81/+-0.10 pg/micrograms protein, n=9) than in extracts from afebrile controls (0.54/+-0.04, n=17). This finding suggests the septum to be the central site of action of alpha-MSH to inhibit fever and further implies a modulatory role of the peptide in the central control of thermoregulation.

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In vitro stimulation of prolactin release by vasoactive intestinal peptide.

The effect of vasoactive intestinal peptide (VIP) on anterior pituitary hormone release was examined in a variety of in vitro preparations. Synthetic VIP was capable of stimulating increased prolactin (PRL) release from male rat hemipituitaries in doses as low as 10-9M only when the enzyme inhibitor bacitracin was present in the incubation medium. Natural porcine VIP was similarly capable of stimulating PRL release, but only at higher doses (10-6M). Additionally, synthetic VIP was capable of stimulating PRL release from dispersed anterior pituitary cells harvested from adult male and lactating female rats and from an enriched population of lactotrophs obtained by unit gravity sedimentation of similar dispersed cells from infantile female rats. No effect of VIP on luteinizing hormone, growth hormone or thyroid stimulating hormone release was seen. These findings taken in concert with the presence of VIP in the hypothalamus, pituitary and hypophyseal portal plasma of the rat suggest a physiological role for VIP in the control of PRL secretion.

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Chromatographic and biologic analysis of ME and OVLT LHRH.

The luteinizing hormone (LH)-releasing activities a pooled rat organum vasculosum lamina terminalis (OVLT) and median eminence (ME) tissues were evaluated for chromatographic and biologic similarity and compared to those of synthetic decapeptide LH-releasing hormone (LHRH). The LHRH detected in these extracts appeared similar chromatographically (Sephadex G-25) to synthetic LHRH. These extracts, as well as synthetic LHRH, were also capable of stimulating dose dependent gonadotropin release form cultures rat gonadotrophs. These findings suggest a physiological role of the LHRH present in the rat OVLT in the control of gonadotropin secretion.

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Intra- and extrahypothalamic luteinizing hormone-releasing hormone (LHRH) distribution in the rat with special reference to mesencephalic sites which contain both LHRH and single neurons responsive to LHRH.

In addition to hypothalamic sites known to contain LHRH, several extrahypothalamic structures in both male and female rats were discovered to contain the decapeptide. In the mesencephalon, the fasciculus retroflexus, interpeduncular nucleus and midbrain central grey contained readily detectable quantities of LHRH. Single neurons responsive to microiontophoretically applied LHRH were also discovered in the mesencephalon suggesting a physiological role for the decapeptide in neuronal events at the level of the midbrain.

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Radioimmunologic localization of vasoactive intestinal polypeptide in hypothalamic and extrahypothalamic sites in the rat brain.

Using a specific radioimmunoassay (RIA), we have quantitated the hypothalamic and extrahypothalamic distribution of vasoactive intestinal polypeptide (VIP) in the rat brain. Highest concentrations of VIP were found in cerebral cortex, suprachiasmatic nucleus, and medial amygdaloid nucleus. Lower concentrations were found in the anterior hypothalamic area, medial preoptic area, peri- and paraventricular nuclei, and hippocampus. Significant levels of VIP were also found in the anterior pituitary. Very little VIP was detected in median eminence and cerebellar cortex. This distribution of VIP in areas of the rat brain known to be important to neuroendocrine function suggests a role for VIP in the control of anterior pituitary events.

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Glucagon-like polypeptides in canine brain.

Glucagon-like material has been detected by radioimmunoassay in several areas of the canine brain. High concentrations of glucagon-like immunoreactivity (GLI), measured with antibodies directed against the N-terminal region of glucagon, have been found in the hypothalamus, amygdala, and mesencephalon, but a high concentration of immunoreactive glucagon (IRG), measured with antibodies directed against the C-terminal region of glucagon, has been found only in the hypothalamus. The predominant molecular forms of GLI isolated from brain extracts by affinity chromatography are the same as those isolated from gut extracts. The predominant form of IRG in brain extracts is of the same (approximate) molecular weight as pancreatic glucagon.

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An antiserum to atrial natriuretic factor (ANF) cross-reacts with neurophysins in the hypothalamo-neurohypophysial system of rat brain.

The distribution of atrial natriuretic factor (ANF)-like reactivity was examined in rat brain and heart by immunohistochemistry. Immunostaining in heart was confined to atrial myocytes. In the hypothalamus, ANF-absorbable immunoreactivity was observed in magnocellular perikarya of the paraventricular and supraoptic nuclei, and in their projections to the neural lobe of the pituitary gland. No staining was seen in the preoptic or arcuate hypothalamic nuclei or in brain stem nuclei as previously reported by other investigators. The patterns of reactivity for ANF reported here is similar to that observed for neurophysins (NPs). Comparison of sequence data between rat ANF-28 and bovine NPs revealed three regions of 3 amino acid homology between these hypothalamic peptides. Preabsorption of the ANF antiserum with Affigel-coupled bovine NP I also resulted in complete elimination of all "ANF-immunoreactivity" in both atrium and hypothalamus. Cross-reactivity of the ANF antiserum with bovine NP I and II was further confirmed by Western blot analysis. Our findings suggest that ANF antisera can cross-react with NPs if they are directed against the shared antigenic epitopes; complete elimination of staining by preabsorption of the antibody with the immunogen, therefore, does not guarantee authenticity of localization. These observations may have relevance to an earlier study which reported on the existence of ANF-immunoreactivity in oxytocin neurons of the hypothalamus.

Amino Acid Sequence↗