Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.
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PMID:Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide. 155 59

Responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide derived from ovine hypothalamus with 68% sequence homology with vasoactive intestinal polypeptide (VIP), were investigated in the pulmonary and hindquarters vascular beds of the anesthetized cat under conditions of controlled blood flow. Injection of the peptide into the perfused lung lobe under elevated tone conditions produced dose-dependent decreases in lobar arterial pressure that were accompanied by biphasic changes in systemic arterial pressure characterized by an initial decrease followed by a secondary increase in pressure. When compared with other vasodilator agents in the pulmonary vascular bed, the relative order of potency was isoproterenol greater than PACAP greater than acetylcholine greater than calcitonin gene-related peptide greater than VIP. In the hindquarters vascular bed, intra-arterial injections of PACAP produced biphasic changes in hindquarters perfusion pressure characterized by initial decreases followed by secondary increases, which were accompanied by biphasic changes in systemic arterial pressure. In terms of relative vasodilator activity in the hindlimb, the order of relative potency was isoproterenol greater than acetylcholine greater than calcitonin gene-related peptide greater than VIP greater than PACAP. PACAP was the only agent that caused a secondary vasoconstrictor response in the hindlimb and produced biphasic changes in systemic arterial pressure. D-Phe2-VIP, a VIP receptor antagonist, blocked the hindquarters vasodilation in response to VIP but had no effect on responses to PACAP. The present investigation shows that PACAP produces pulmonary vasodilation, as well as dilation, and vasoconstriction in the systemic (hindlimb) vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of PACAP and VIP on the pulmonary and hindquarters vascular beds of the cat. 156 76

Age-related changes in the human peripheral sudomotor neuro-effector system have been investigated in six 80-year-olds and six young adults. Histochemical and immunohistochemical studies on forearm skin biopsies showed diminished vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP)-like immunoreactivity and a virtual absence of acetylcholinesterase in the elderly sudomotor nerve endings compared to the young. Reduced size of nerve bundles and decreased density of sympathetic nerve endings adjacent to the sweat glands of old people were shown by the neuronal marker, protein gene product (PGP 9.5), and by electron microscopy. Image analysis techniques were also used to demonstrate a marked regression in secretory coil size with age. Functional decrements accompanying the neurochemical and morphological changes in the neuro-effector system were measured in ten 80-year-olds by local quantitative nicotine axon reflex responses and compared with 12 young adults. These studies demonstrate marked regressive changes in both the nerve endings and target cells in old age and appear to express a significant loss of vigour in trophic interactions.
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PMID:Immunohistochemical, morphological and functional changes in the peripheral sudomotor neuro-effector system in elderly people. 158 96

The existence, distribution and density of various neuropeptides in human submandibular and parotid glands were investigated using immunocytochemistry and radioimmunoassay. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide Y (NPY) and C-flanking peptide of NPY (CPON) immunoreactivities (ir) were found in close association to acini, ducts and blood vessels. Only few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated, mainly localized around blood vessels and ducts. Galanin and the newly discovered peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP) could not be detected in human salivary glands.
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PMID:Neuropeptides in human salivary (submandibular and parotid) glands. 160 4

Atypical carcinoid tumor of the lung with amyloid stroma seen in a 43-year-old woman is reported. The 47 x 45 x 33 mm tumor, located at the periphery of the S8 segment of the resected left lower lobe, revealed Dylon-positive amyloid deposition in the stroma. The argyrophilic tumor cells with occasional mitoses and focal venous involvement predominantly showed immunoreactivity of cytokeratin, neuron-specific enolase, cystatin C, chromogranin A, calcitonin and neuropeptide Y (NPY). Fewer cells were immunoreactive for calcitonin gene-related peptide (CGRP), the alpha-subunit of human chorionic gonadotropin, gastrin-releasing peptide, serotonin, methionine-enkephalin and gastrin. Immunoreactive CGRP or NPY were co-localized in calcitonin-positive cells. The amyloid substance was positively labeled only for CGRP. Immunostaining for amylin, a polypeptide isolated from insular amyloid in type II diabetes mellitus or insulinoma showing a 50% homology with CGRP, was negative. The specificity of immunostaining for calcitonin, CGRP and amylin was confirmed by immunoabsorption tests using synthetic human antigens. Immunoelectron microscopic studies disclosed peptide localization in neurosecretory-type granules and CGRP immunoreactivity in extracellular amyloid fibrils. This is the first report describing CGRP as a component of amyloid of endocrine origin.
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PMID:Atypical carcinoid tumor of the lung with amyloid stroma. 160 16

The peptidergic innervation of rat thymus has been investigated by immunohistochemical methods, focusing on the spatial interrelationship of peptidergic nerve fibers with mast cells and macrophages in the rat. An antiserum directed against the protein gene product 9.5 (PGP 9.5) regarded as a pan-neuronal marker revealed a rich innervation, especially in the subcapsular cortex, in interlobular septa, and of the vasculature in the cortex and the corticomedullary boundary. A minor proportion of PGP 9.5-immunoreactive (ir) fibers supplied the thymic parenchyma. The main component of peptidergic innervation consisted of fibers costaining for tachykinins (TKs) and calcitonin gene-related peptide (CGRP), but considerable amounts of neuropeptide Y (NPY)/tyrosine hydroxylase (TH)-positive fibers and vasoactive intestinal polypeptide/peptide histidine isoleucine-positive fibers also were present. There were sparse Leu-enkephalin and galanin immunoreactivities in thymic nerve fibers, while neurotensin was absent from nerve fibers. Close associations of TK/CGRP-ir and NPY-ir fibers with mast cells were frequently detected in the connective tissue areas of the thymus, often adjacent to the vasculature. TK/CGRP-ir fibers and some rare NPY-ir fibers were found adjacent to EDl-positive macrophages and less frequently to mast cells. TK/CGRP-ir and NPY-ir fibers were mainly detected in relation to the vasculature of the cortex and the corticomedullary boundary, but also were found in capsular and subcapsular regions of the thymic cortex. The possible importance of the close spatial relationship between the various peptide-containing nerve fibers and mast cells and ED1-positive macrophages in neuroimmune integration is discussed.
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PMID:Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus. 164 85

Calcitonin gene-related peptide is a putative neurotransmitter of central and peripheral nervous systems which coexists with acetylcholine in motor nerve terminals and exerts multiple effects on skeletal muscle, suggesting a trophic role for this neuropeptide. Using radiolabeled calcitonin gene-related peptide as a probe in a specific binding assay, we have characterized calcitonin gene-related peptide binding sites on chick skeletal muscle membranes. Binding is time-dependent, saturable and reversible. Scatchard analyses revealed two classes of sites: high-affinity sites with a KD value of 62 pM, and low-affinity sites with a KD value of 3.3 nM. The maximal number of sites is, respectively, 22 and 155 fmol/mg protein for high- and low-affinity binding sites. Specific binding was not affected by the presence, in excess, of other neuropeptides such as salmon calcitonin or somatostatin or vasoactive intestinal polypeptide. Affinity of the binding site for calcitonin gene-related peptide was decreased in the presence of 5'-guanylyl-imidodiphosphate, suggesting a physiological coupling of calcitonin gene-related peptide receptor to a GTP binding protein. In a developmental study of chick muscle, we found the highest activity of calcitonin gene-related peptide binding sites in 11-14 day embryos, following a pattern of evolution similar to that of acetylcholine receptors (constant ratio of 12 acetylcholine receptors per calcitonin gene-related peptide binding site). However, both receptors appear differentially regulated: while the number of acetylcholine receptors increases 5-16-fold after denervation, calcitonin gene-related peptide binding sites slightly diminish in number. These results are discussed in terms of the physiological significance of calcitonin gene-related peptide binding sites on chick skeletal muscle membrane.
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PMID:Characterization and developmental evolution of a high-affinity binding site for calcitonin gene-related peptide on chick skeletal muscle membrane. 165 62

Right ventricular myocardium was assessed for cholinergic and adrenergic innervation, as well as alpha-adrenergic, beta-adrenergic, and muscarinic receptors, in 18 cyanotic patients with tetralogy of Fallot (TOF) and four acyanotic control patients with ventricular septal defect, each of whom underwent a cardiac repair from June through December 1987. Neurons containing acetylcholine (ACH), neuron-specific enolase (NSE), S-100 protein, neuropeptide-Y (NPY), dopamine-beta-hydroxylase (DBH), and calcitonin gene-related polypeptide (CGRP) were detected surrounding arterioles and myocytes in all specimens. NSE and S-100 immunoreactivities were also identified in the cytoplasm of TOF cardiocytes, possibly indicating a neuroendocrine origin of these cells. Cardiocyte size was increased in TOF (p = 0.05). Acetylcholine (cholinergic) (p = 0.04) and CGRP (cholinergic) positive neurons (p = 0.07) were decreased in the TOF as compared to controls. Adrenergic fiber content (p = 0.15) and beta receptors (p = 0.21) were similar in both groups. There was an increase in muscarinic receptors in the controls (p = 0.002), and a marked increase in alpha receptors in TOF (p = 0.019). There were no intragroup differences in the TOF patients according to degree of cyanosis. In conclusion, there were important differences in neuronal and amine receptor content between TOF and control patients. Increased alpha receptors in TOF could account for differences in clinical and hemodynamic events.
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PMID:Determination of infundibular innervation and amine receptor content in cyanotic and acyanotic myocardium: relation to clinical events in tetralogy of Fallot. 165 27

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. We have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in two human inflammatory diseases, ulcerative colitis and Crohn's disease, using quantitative receptor autoradiography. The sensory neurotransmitter receptors included bombesin, calcitonin gene-related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only binding sites for substance P and vasoactive intestinal peptide were significantly altered in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.
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PMID:Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. 165 49

The effect of capsaicin was studied in precontracted longitudinal muscle strips of the rat gastric fundus. Capsaicin induced a relaxation in the concentration range 10(-7)-10(-6) M. The relaxation induced by 10(-6) M capsaicin was completely prevented by extrinsic denervation of the stomach. The adrenoceptor antagonists phentolamine and propranolol did not influence the effect of capsaicin while hexamethonium potentiated it; this potentiation was not observed with another nicotinic receptor antagonist trimethaphan. Tetrodotoxin did not have a consistent effect as it reduced the capsaicin-induced relaxation in some but not all tissues. The peptidase trypsin consistently reduced the action of capsaicin but vasoactive intestinal polypeptide (VIP) antiserum, desensitization to calcitonin gene-related peptide (CGRP), and CGRP antiserum had no influence. The neuropeptide involved in the relaxant effect of capsaicin in the rat gastric fundus has thus still to be determined.
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PMID:Relaxant effect of capsaicin in the rat gastric fundus. 167 77


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