Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution, ontogeny and fiber projections of cholecystokinin-8, vasoactive intestinal polypeptide and gamma-aminobutyrate-containing neuronal systems in the rat spinal cord were investigated by means of immunocytochemistry. Immunoreactive fibers to cholecystokinin-8, vasoactive intestinal polypeptide and glutamate decarboxylase (gamma-aminobutyrate-synthesizing enzyme, used as a marker of gamma-aminobutyrate) were widely distributed in the spinal cord, being particularly concentrated in the superficial dorsal horn, suggesting a close relationship to the pain transmission system. Cholecystokinin-8-containing neurons were mostly distributed in the dorsal laminae and glutamate decarboxylase-containing neurons were distributed in both the dorsal and ventral horns. Vasoactive intestinal polypeptide-containing neurons were detected in the lateral spinal nucleus and the lamina X. Cholecystokinin-8 and vasoactive intestinal polypeptide immunoreactive structures first appeared on gestational day 17-18. Although no substantial change in immunoreactive structures was observed during the fetal period, they increased markedly after birth. On the other hand, glutamate decarboxylase-positive structures appeared at gestational day 16 and those in the grey matter reached a maximum content at birth; both groups were present in adult animals. Transection of the upper cervical cord resulted in accumulations of cholecystokinin-8 and glutamate decarboxylase rostral to the lesion, revealing the presence of supraspinal projections of cholecystokinin-8 and glutamate decarboxylase to the spinal cord. The same experimental procedure demonstrated the existence of vasoactive intestinal polypeptide-mediating neuronal projections to the supraspinal level, as the accumulating fibers occurred in the area caudal to the lesion.
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PMID:Distribution, ontogeny and projections of cholecystokinin-8, vasoactive intestinal polypeptide and gamma-aminobutyrate-containing neuron systems in the rat spinal cord: an immunohistochemical analysis. 388 8

Plasma from persons with hereditary angioneurotic edema readily developed the capacity to increase vascular permeability and to induce the isolated rat uterus to contract. Both activities resided in a small, heat-stable molecule that was apparently a polypeptide. Crude preparations of the polypeptide were inactivated during incubation with trypsin. They also failed to produce pain and erythema, but caused markedly increased vascular permeability in human skin. These characteristics differ from those of bradykinin, from which crude preparations of the polypeptide could also be distinguished by electrophoretic mobility and paper chromatographic behavior. Proof that the polypeptide is truly different from bradykinin must await its further purification. Histamine played no role in the activities observed. Although the enzymes functioning to release the permeability factor and kinin activities in hereditary angioneurotic edema plasma were not clearly defined, one or more plasma enzymes other than C'1 esterase presumably participated either in conjunction with C'1 esterase or in pari passu events to release the polypeptide mediating these activities.
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PMID:Permeability-increasing activity in hereditary angioneurotic edema plasma. II. Mechanism of formation and partial characterization. 581 21

To date about thirty peptides--low-molecular-weight, single-chain amino acid compounds--are known to be distributed widely in the central nervous system within selective neuron pathways. These findings, combined with a large body of neuropharmacological, behavioral, and electrophysiological data, open new horizons in neurobiology, force a reexamination of old and accepted hypotheses, and hold important implications for the clinician. There is evidence that substance P and the opioid peptides play a major role in the pain pathway, particularly at the level of the spinal cord. Available evidence also implicates vasoactive intestinal polypeptide in the control of cerebral circulation, cholecystokinin in the regulation of appetite, and vasopressin and adrenocorticotropic hormone in memory. Many questions, however, remain. For most peptides there is little information on mechanisms of biosynthesis, release, interaction with receptors, and termination of biological effect. Another important question is the interaction of peptides with other neurotransmitters. The evidence that both "classic" neurotransmitters and peptides can be found in the same neuronal necessitates reformulation of Dale's "one neuron, one neurotransmitter" hypothesis. It may be that a single cell, while containing different classes of neurotransmitter, will contain only one member of any particular class. It is not too early to speculate on the role of the numerous and diverse peptides in neuronal tissue and on the implications of peptide abnormalities in a variety of neurological diseases. The answers to these and other questions pose a fascinating challenge to neurobiologist and clinician alike.
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PMID:Neuroendocrinology and brain peptides. 616 92

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.
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PMID:Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine. 618 98

Despite the important contribution of the midbrain periaqueductal gray (PAG) to endogenous pain suppression systems, little is known about the neuroanatomical basis of its functional organization. In a previous study of the distribution of the endogenous opiate leucine-enkephalin (ENK) in the PAG (Moss, M. S., E. J. Glazer, and A. I. Basbaum (1983) J. Neurosci. 3: 603-616), we found that immunoreactive ENK-containing neurons and terminals are clustered in discrete populations. In this study we have extended our analysis of the neurochemical organization of the PAG by using immunocytochemistry to map the distribution of two non-opiate peptides that produce potent analgesia when administered at central gray levels: substance P (Sub P) and vasoactive intestinal polypeptide (VIP). Immunoreactive Sub P neurons and terminal fields are clustered in discrete populations throughout the PAG. The distribution pattern of these populations changes at different rostral-caudal levels of the PAG. For example, there is a ventral-to-dorsal shift in the location of Sub P-like immunoreactivity from the caudal to the rostral PAG. Few immunoreactive Sub P neurons are found in the nucleus raphe dorsalis although moderately dense terminal field staining is present. The staining pattern of immunoreactive VIP is totally different from that of Sub P. Regardless of the rostral-caudal level examined, VIP-containing neurons are found tightly clustered in the subependymal neuropil of the ventromedial PAG. Only a few immunoreactive VIP-containing neurons are found in the ventral PAG or nucleus raphe dorsalis. The striking differences between the distribution of Sub P- and VIP-like immunoreactivity in the PAG indicates that the neural circuitry underlying pain suppression by Sub P and VIP may also differ.
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PMID:The peptidergic organization of the cat periaqueductal gray. II. The distribution of immunoreactive substance P and vasoactive intestinal polypeptide. 619 Oct 12

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6

The knowledge of the amino acid sequence of both beta-lipotropin (beta-LPH) and gamma-LPH was the starting point that led to the hypothesis, considered revolutionary in 1967, that hormonal precursors exist. This concept was simultaneously proposed for proinsulin and applied later to other polypeptide hormones. The discovery of endorphins brought together two fields of research that were not related: the opiates and the so-called pituitary lipotropic hormones. The demonstration of specific brain opiate receptors led to the hypothesis of the existence of endogenous opiate ligands which could act as neurotransmittors. The isolation of such substances in the brain, first named enkephalins, revealed through their amino acid sequence their structural homology with the pituitary lipolytic hormones. The finding of a more potent opioid substance in the pituitary (beta-endorphin) that comprises the last 31 amino acids of beta-LPH shed a new light on the hypothesis proposed earlier which gave to beta-LPH a role as a precursor molecule. Finally, the addition of ACTH completed a putative multipotent precursor model that has been recently named pro-opiomelanocortin. Pulse-chase experiments have definitely proven that beta-endorphin is a maturation product of a large precursor also containing ACTH and MSH. In other studies, many groups have suggested that endorphins play important roles as possible neuromodulators in pain transmission, in analgesia, in tolerance and dependence, as well as on behavior and endocrine regulations, mainly those related to the hypothalamo-pituitary axes. The elucidation of the biosynthetic process or processes of cerebral endorphins (either enkephalins or beta-endorphin) is of primary importance in order ot understand better their biological as well as regulatory functions. These studies should also be applicable to the biosynthesis of all the other neuronal peptide hormones. It is hoped that they will provide new tools for the study of some important central nervous system functions, such as pain and endocrine control and the physiopathology of behavioral diseases.
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PMID:[Endorphins: structure, roles and biogenesis]. 626 34

It has been proposed that the polypeptide calcitonin (CT) occurs in the central nervous system and may have a neuromodulatory role in endogenous pain relief pathways. However, recent results suggest that CT is not present in the central nervous system. Intrathecal (IT) injection of CT on the lumbar enlargement of rats caused a reversible increase of the hindpaw lick latency in the hot plate test. No analgesia was observed with the vocalization test to electrical stimulation of the tail. In contrast 10 micrograms morphine hydrochloride IT caused analgesia in both tests. It is concluded that IT CT does not cause analgesia, but has a reversible blocking effect on motor responses.
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PMID:Subarachnoid injection of salmon calcitonin does not induce analgesia in rats. 649 28

Eukaryotic cell polypeptide chain initiation factor eIF-2 forms ternary complexes with GTP and initiator Met-tRNAf. These complexes can be destabilized in vitro by the addition of salt-washed 40S ribosomal subunits. Our evidence suggests that this destabilization is mediated by GDP generated by premature hydrolysis of the GTP molecule present in the ternary complex. With complexes formed by using a partially purified preparation of eIF-2 from Ehrlich ascites tumor cells, it is possible to reverse the 40S subunit induced inhibition by creating conditions which eliminate free GDP from the system. This reversal probably occurs due to exchange of GTP for the GDP bound to the initiation factor, in a reaction catalyzed by another factor present in the eIF-2 preparation. However, if the eIF-2 has previously been phosphorylated by the reticulocyte heme-controlled repressor, the 40S subunit induced inhibition cannot be reversed by elimination of free GDP. The instability of initiation complexes containing eIF-2, together with the impairment of guanine nucleotide exchange after phosphorylation of eIF-2 [Clemens, M.J., Pain, V.M., Wong, S.-T., & Henshaw, E. C. (1982) Nature (London) 296, 93-95], may be an important aspect of the mechanism of the inhibition of translation by the heme-controlled repressor.
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PMID:Assembly and breakdown of mammalian protein synthesis initiation complexes: regulation by guanine nucleotides and by phosphorylation of initiation factor eIF-2. 655 Nov 77

Formation of the ternary complex Met-tRNAi X eukaryotic initiation factor (eIF) 2 X GTP from eIF-2 X GDP requires exchange of GDP for GTP. However, at physiological Mg2+ concentrations, GDP is released from eIF-2 exceedingly slowly (Clemens, M.J., Pain, V.M., Wong, S.T., and Henshaw, E.C. (1982) Nature (Lond.) 296, 93-95). However, GDP is released rapidly from impure eIF-2 preparations, indicating the presence of a GDP/GTP exchange factor. We have now purified this factor from Ehrlich cells and refer to it as GEF. CM-Sephadex chromatography of ribosomal salt wash separated two peaks of eIF-2 activity. GEF was found in association with eIF-2 in the first peak and co-purified with eIF-2 under low salt conditions. It was separated from eIF-2 in high salt buffers and further purified on hydroxylapatite and phosphocellulose. Gel electrophoresis of our purest preparations showed major bands at 85, 67, 52, 37, 27, and 21 kDa. Purified GEF increased the rate of exchange of [32P] GDP for unlabeled GDP 25-fold but did not function with phosphorylated eIF-2 (alpha subunit). The factor also stimulated markedly the rate of ternary complex formation using eIF-2 X GDP as substrate with GTP and Met-tRNAi but not using phosphorylated eIF-2 X GDP as substrate. eIF-2 is released from the 80 S initiation complex with hydrolysis of GTP. If eIF-2 X GDP is actually the complex released, then GEF is absolutely required for eIF-2 to cycle and it is therefore a new eukaryotic initiation factor. Furthermore, the inability of GEF to utilize eIF-2 (alpha P) X GDP explains how phosphorylation of eIF-2 can inhibit polypeptide chain initiation.
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PMID:A GDP/GTP exchange factor essential for eukaryotic initiation factor 2 cycling in Ehrlich ascites tumor cells and its regulation by eukaryotic initiation factor 2 phosphorylation. 655 52


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