Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various neurogenic peptides and neurotransmitter substances on the release of ACTH induced by hypothalamic corticotropin releasing factor (HY-CRF) were investigated using monolayer cultured anterior pituitary cells. Test substances were given in combination with 0.05-0.1 hypothalamic extract (HE)/ml, because HE evoked a significant ACTH release and a linear dose response relationship was demonstrated sequentially between 0.0165 HE/ml and 0.5 HE/ml. Relative high doses of lysine-vasopressin showed a slight additive effect on the release of ACTH induced by 0.1 HE/ml. Leu-enkephalin, dopamine, prostaglandin E1 and E2 slightly reduced the release of ACTH induced by HY-CRF, but the inhibitory effect of these substances were not dose-related. Other tested substances including luteinizing hormone releasing hormone, thyrotropin releasing hormone, somatostatin, melanocyte stimulating hormone release inhibiting factor, beta-endorphin, neurotensin, substance P, vasoactive intestinal polypeptide, angiotensin II, norepinephrine, serotonin, acetylcholine, histamine and gamma-amino butyric acid showed neither agonistic nor antagonistic effect on the release of ACTH induced by HY-CRF. These results indicate that the release of ACTH is controlled specifically by HY-CRF and corticosterone, and modified slightly by some other substances such as vasopressin and prostaglandins, and that the effect of most other neurogenic peptides and neurotransmitter substances is negligible or non-physiological at the pituitary level.
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PMID:ACTH release in pituitary cell cultures. Effect of neurogenic peptides and neurotransmitter substances on ACTH release induced by hypothalamic corticotropin releasing factor (CRF). 3 43

Biologically active peptides and neurotransmitter substances were added to anterior pituitary cell cultures to examine the presence of corticotropin releasing factor (CRF)-like activity. Hypothalamic extract (HE) induced significant dose-related increase of ACTH, and the lowest effective dose was 0.01 HE/ml. Other tested substances including luteinizing hormone-releasing hormone, thyrotropin releasing hormone, melanocyte stimulating hormone release inhibiting factor, somatostatin, substance P, neurotensin, beta-endorphin. leu-enkephalin, met-enkephalin, bradykinin, norepinephrine, dopamine, serotonin, acetylcholine, histamine, gamma-amino butyric acid or gamma-hydroxy butyric acid showed no CRF-like activity. Relatively high doses of lysine vasopressin, arginine vasopressin and angiotensin II increased the release of ACTH in pituitary cell cultures, but the maximal ACTH response was markedly less than with HE. These results indicate that cultured anterior pituitary cells are sensitive and fairly specific in detecting CRF(s) comparing with other detecting procedures.
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PMID:Specificity of cultured anterior pituitary cells in detecting corticotropin releasing factor(s): the effect of biologically active peptides and neurotransmitter substances on ACTH release in pituitary cell cultures. 3 34

Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent. Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors. Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli. Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall- and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats. Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats. CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites. We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH. In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation. Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site. These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis. These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems.
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PMID:Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis. 128 40

Tumor tissue located in the occipital lobe with hemorrhage was obtained from a 19-year-old patient. Histological examination indicated it to consist of undifferentiated small, round cells without neuronal or glial differentiation, and possibly to be a type of primitive neuroectodermal tumor. The tumor cells were cultured for 3 years and a continuous cell line (KK-2) was established. KK-2 was transplantable to nude mice. With immunocytochemistry, neuron-specific enolase, protein gene product 9.5, vimentin, TUJ1 (a monoclonal antibody specific for neuron-associated class III beta-tubulin isotype) and 6H7 (a monoclonal antibody to NCAM produced by us) were detected. None of the following could be found: glial fibrillary acidic protein, S-100 protein, neurofilament and synaptophysin, calcitonin gene-related peptide, gastrin releasing peptide corticotropin-releasing factor, substance P, somatostatin, chromogranin, aromatic L-amino acid decarboxylase and tyrosine hydroxylase. The original tumor and KK-2 cells obtained after 3 years of culture and transplants in nude mice displayed essentially the same ultrastructural and immunohistochemical characteristics. KK-2 cells showed no differentiation to mature neuronal, glial or ependymal cells. This cell line may possibly serve as a useful model for studying cellular differentiation of human neuroectodermal tumors and normal neuronal development.
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PMID:A continuous cell line (KK-2) from a supratentorial primitive neuroectodermal tumor. 132 7

Superior cervical ganglia from 7 human cadavers (3-7 h post mortem) were immunostained for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and 14 different neuropeptides. The results show that ganglionic cells contain TH, DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). These substances were present predominantly within large ganglionic cells. Inside the ganglion, the number and topographical distribution of various types of immunoreactive cells differed from one another. NPY and CGRP immunoreactivities were found in some TH-positive cells, but that co-localization never exceeded the 30% of the TH cells. Leu-enkephalin showed a weak immunoreactivity, which was restricted to fibers or varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin, galanin, corticotropin-releasing factor, thyrotropin-releasing hormone, angiotensin II and neurotensin showed no immunoreactivity in the human superior cervical ganglion.
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PMID:Neuropeptides in the human superior cervical ganglion. 135 73

The central amygdaloid nucleus (ACe) is part of the amygdaloid body, and it has been shown to participate in several stress related reactions. The ACe is densely innervated by tyrosine hydroxylase- (TH), corticotropin releasing factor- (CRF), calcitonin gene-related peptide- (CGRP), neurotensin- (NT), somatostatin- (SOM), enkephalin- (ENK), substance P- (SP), vasoactive intestinal polypeptide- (VIP) and cholecystokinin- (CCK) immunoreactive (IR) nerve terminals. In addition, the ACe contains numerous CRF-, NT-, SOM-, ENK- and SP-IR perikarya. In previous studies it has been shown that stress stimulates the expression of the immediate early gene c-fos in the ACe. The aim of this study was to demonstrate the colocalization of the Fos-IR neurons with the peptide- and TH-IR structures using an immunocytochemical double staining technique. In intact animals the ACe contained only a few Fos-IR neurons. After immobilization stress about 100 Fos-IR neurons were seen per section. They were mainly located in the area, which was enriched by peptide- and TH-IR nerve terminals. The close contacts observed between the Fos-IR neurons and the peptide- and TH-IR nerve endings suggest that the Fos-IR neurons were innervated by these nerve terminals. Furthermore, several NT-, ENK-, SOM- and CRF-IR neurons were observed and the vast majority of these cells exhibited Fos-like immunoreactivity. These results suggest that stress enhances the synaptic activity of the ACe, which stimulates the expression of c-fos. Subsequently, Fos may regulate the expression of the NT, ENK, SOM and CRF genes and thus affect the peptidergic efferents from the ACe.
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PMID:Colocalization of peptide- and tyrosine hydroxylase-like immunoreactivities with Fos-immunoreactive neurons in rat central amygdaloid nucleus after immobilization stress. 136 16

The central nucleus of the amygdala, bed nucleus of the stria terminalis, and central gray are important components of the neural circuitry responsible for autonomic and behavioral responses to threatening or stressful stimuli. Neurons of the amygdala and bed nucleus of the stria terminalis that project to the midbrain central gray were tested for the presence of peptide immunoreactivity. To accomplish this aim, a combined immunohistochemical and retrograde tracing technique was used. Maximal retrograde labeling was observed in the amygdala and bed nucleus of the stria terminalis after injections of retrograde tracer into the caudal ventrolateral midbrain central gray. The majority of the retrogradely labeled neurons in the amygdala were located in the medial central nucleus, although many neurons were also observed in the lateral subdivision of the central nucleus. Most of the retrogradely labeled neurons in the BST were located in the ventral and posterior lateral subdivisions, although cells were also observed in most other subdivisions. Retrogradely labeled neurotensin, corticotropin releasing factor (CRF), and somatostatin neurons were mainly observed in the lateral central nucleus and the dorsal lateral BST. Retrogradely labeled substance P-immunoreactive cells were found in the medial central nucleus and the posterior and ventral lateral BST. Enkephalin-immunoreactive retrogradely labeled cells were not observed in the amygdala or bed nucleus of the stria terminalis. A few cells in the hypothalamus (paraventricular and lateral hypothalamic nuclei) that project to the central gray also contained CRF and neurotensin immunoreactivity. The results suggest the amygdala and the bed nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin, somatostatin, and substance P terminals in the midbrain central gray.
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PMID:Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat. 138 26

The hypothalamo-neurohypophyseal tract is known to contain the classical neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin, methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), and galanin are co-stored with vasopressin and/or oxytocin. Recent immunohistochemical studies have revealed the existence of a low to moderate number of substance P-, vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were distributed throughout the organ, whereas somatostatin-immunoreactive fibers were present in the proximal part of the organ. The positive nerve endings were either large in size resembling classical nerve terminals related to perivascular spaces, or smaller similar to peptidergic fibers as described in the CNS. These results indicate that these neuropeptides may be either co-stored with the classical neurohypophyseal hormones or contained in another system of afferents to the organ. The probably distinct functional roles of these neuropeptides in the physiology of the neurohypophysis are discussed.
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PMID:Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo-neurohypophyseal tract: experimental immunohistochemical studies. 138 83

In the present study, we determined that rat mononuclear leukocytes possess specific receptors for growth hormone releasing hormone (GHRH). The results show that the binding of 125I-labeled GHRH to spleen and thymic cells was saturable and of a high affinity, approximately 3.5 and 2.5 nM for thymus and spleen cells, respectively. The Scatchard analysis revealed a binding capacity of approximately 54 and 35 fmol per 10(6) cells on thymus and spleen, respectively. The binding of GHRH was not competed by 10(-6) M growth hormone, corticotropin releasing factor, substance P or luteinizing hormone releasing hormone and vasointestinal peptide (VIP). Partial characterization of the receptor was accomplished by crosslinking 125I-labeled GHRH to thymus cells with disuccinimidyl suberate and polyacrylamide gel electrophoresis. Autoradiography of dried gels showed two major components in leukocytes and pituitary cells at approximately 42 and 27 kDa which could be diminished by unlabeled GHRH. The treatment of leukocytes with GHRH (10 nM) rapidly increased the intracellular free calcium concentration from a basal level of 70 +/- 20 nM to a plateau value of 150 +/- 20 nM in 6 min after stimulation. The functional activity of GHRH receptors was studied further by measuring lymphocyte proliferative responses and the increase in the level of cytoplasmic GH RNA. The presence of GHRH alone resulted in a dose-dependent increase in thymidine and uridine incorporation and a dose-dependent increase in the levels of GH RNA in the cytoplasm. Taken together, the results show that lymphocytes contain specific receptors for GHRH that are coupled to important biological responses and further support the concept of bidirectional communication between the immune and neuroendocrine tissues.
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PMID:Growth hormone releasing hormone receptors on thymocytes and splenocytes from rats. 171 93

The knowledge on the neuronal inputs to the locus coeruleus (LC) and their roles in regulating noradrenergic (NA) cellular activity is quite advanced. In recent years, however, about ten neuropeptides were found to be localized in the area of the rodent LC; peptides which may be considered as potential transmitters or modulators acting in this area. Electrophysiological studies performed in vivo and in vitro have revealed that many of these peptides are able to alter LC neuronal activity. Stimulatory effects have been described with vasopressin, substance P, adrenocorticotropin hormone and corticotropin-releasing factor. Depressant effects were seen with galanin, somatostatin, neuropeptide Y and enkephalin. Variable actions were observed in the case of neurotensin. While these findings point to a possible regulatory function of these peptides in this area, precise roles remain unclear. Important information is lacking that would conclusively demonstrate their regulatory functions. It should be determined whether the stimulation of peptidergic cells elicits synaptic effects identical to the ones observed with local exogenous peptide applications. By studying the action of blockers of these transmitter and modulator candidates, we would probably begin to understand their importance in the regulation of tonic and phasic activity components. The LC is generally considered to consist of a homogenous group of neurons. The recent observation that subpopulations of these cells contain peptides as in the case of neuropeptide Y, galanin and vasopressin, points to the possible existence of subgroups of neurons having different functions.
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PMID:Responses of locus coeruleus neurons to neuropeptides. 181 23


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