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)

CCK-octapeptide (CCK-8) (EC50 = 0.5 nM), in the presence of Li+, increased 3H-inositol phosphate (IP) accumulation in guinea pig gastric glands prelabeled with 3H-inositol. CCK-8 desulfate, human gastrin I and pentagastrin were much less potent than CCK-8. Antagonists of CCK receptors such as proglumide, dibutyryl-c-GMP and CBZ-Tyr (SO3H)-Met-Gly-Trp-Met-AspNH2 shifted the CCK dose response curve to the right. However, histamine (H1 and H2), cholinergic, substance P and alpha- and beta-adrenergic receptor antagonists had no effect on 3H-IP accumulation induced by CCK. The results suggest that CCK receptor activation in gastric glands leads to an enhanced breakdown of inositol phospholipids which may relate to calcium mobilization and pepsinogen secretion.
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PMID:Cholecystokinin receptor mediated hydrolysis of inositol phospholipids in guinea pig gastric glands. 298 60

Gastrin-releasing peptide (GRP) labeled with 125I at tyrosine-15 (125I-GRP) binds to intact quiescent Swiss 3T3 cells in a specific and saturable manner. Scatchard analysis indicates the presence of a single class of high-affinity binding sites of Kd = 0.5 X 10(-9) M and a value for the number of sites per cell of about 100,000. 125I-GRP binding was not inhibited by other mitogens for these cells, and cell lines that are mitogenically unresponsive to GRP do not exhibit specific GRP binding. Structure-activity relationships show a close parallel between the ability of a range of GRP-related peptides to both inhibit GRP binding and to stimulate mitogenesis. Further, GRP binding is selectively blocked in a competitive fashion by a novel bombesin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11] substance P. In addition, this compound selectively inhibits GRP and bombesin-induced mitogenesis. These results demonstrate that the mitogenic response of Swiss 3T3 cells to peptides of the bombesin family is mediated by a class of receptors distinct from those of other mitogens for these cells.
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PMID:High-affinity receptors for peptides of the bombesin family in Swiss 3T3 cells. 299 72

Both directly acting (GABAA and GABAB agonists) and indirectly acting GABAergic agents (GABA uptake inhibitors and GABA-transaminase inhibitors) produce analgesia in a variety of animal test systems. Analgesia produced by GABAA agonists is probably due to a supraspinal action, although spinal sites may also play a role. GABAA agonist analgesia is insensitive to naloxone, bicuculline, picrotoxin and haloperidol, but is blocked by atropine, scopolamine and yohimbine suggesting a critical role for central cholinergic and noradrenergic pathways in this action. The lack of blockade by the GABAA antagonist bicuculline is difficult to explain. Both bicuculline and picrotoxin have intrinsic analgesia actions which may not necessarily be mediated by GABA receptors. The GABAB agonist baclofen produces analgesia by actions at both spinal and supraspinal sites. Baclofen analgesia is insensitive to naloxone, bicuculline and picrotoxin, and blockade by cholinergic antagonists occurs only under limited conditions. Catecholamines are important mediators of baclofen analgesia because analgesia is potentiated by reserpine, alpha-methyl-p-tyrosine, phentolamine, ergotamine, haloperidol and chlorpromazine. A role for serotonergic mechanisms is less well defined. Methylxanthines, which produce a clonidine-sensitive increase in noradrenaline (NA) turnover, increase baclofen analgesia by a clonidine-sensitive mechanism. Both ascending and descending NA pathways are implicated in the action of baclofen because dorsal bundle lesions, intrathecal 6-hydroxydopamine and medullary A1 lesions markedly decrease baclofen analgesia. However, simultaneous depletion of NA in ascending and descending pathways by locus coeruleus lesions potentiates baclofen analgesia suggesting a functionally important interaction between the two aspects. Baclofen analgesia within the spinal cord may be mediated by a distinct baclofen receptor because GABA does not mimic the effect of baclofen and the rank order of potency both of close structural analogs of baclofen as well as antagonists differs for analgesia and GABAB systems. The spinal mechanism may involve an interaction with substance P (SP) because SP blocks baclofen analgesia, and desensitization to SP alters the spinal analgesic effect of baclofen. GABA uptake inhibitors produce analgesia which is similar to that produced by GABAA agonists because it is blocked by atropine, scopolamine and yohimbine. Analgesia produced by GABA-transaminase inhibitors is similar to that produced by GABAA agonists because it can be blocked by atropine, but it is potentiated by haloperidol while THIP analgesia is not.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABAergic mechanisms of analgesia: an update. 303 1

A photoreactive (D-Ala2, p-N3-Phe4-Met5)enkephalin derivative was prepared, iodinated with carrier-free 125I, and then purified by high-performance liquid chromatography. The purified radioactive photoprobe was monoiodinated at the amino terminal tyrosine residue. This radioactive photoprobe was used to photoaffinity label membranes prepared from the rat brain (minus cerebellum) and the spinal cord. The photolabeled membranes were analyzed by sodium dodecyl sulfate gel electrophoresis. A 46,000-Da protein was specifically photolabeled in these membrane preparations. The photolabeling of this protein was inhibited by peptides related to enkephalin but not by unrelated substance P or gastrin tetrapeptide. A concentration-dependent inhibition of the photolabeling of the 46,000-Da protein was observed in the presence of competing ligands specific for the mu-, delta-, and kappa-opioid receptors. These data demonstrate that the radioactive photoprobe labels the mu-, delta-, and kappa-opioid receptors. Although there is no evidence available to show that the 46,000-Da protein is identical in all the cases, our data strongly suggest that it is a binding protein common to all of the opioid receptor subtypes.
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PMID:Photoaffinity labeling of opioid receptor of rat brain membranes with 125I(D-Ala2, p-N3-Phe4-Met5)enkephalin. 303 63

The distribution of FMRFamidelike peptides was studied in the nervous system of the lobster Homarus americanus by using immunocytochemical and radioimmunological techniques. By radioimmunoassay FMRFamidelike immunoreactivity (FLI) was found in low levels (ca. 1 pmol/mg protein) throughout the ventral nerve cord and in much higher amounts (60-100 pmol/mg protein) in the neurosecretory pericardial organs. Immunocytochemical studies showed FLI in approximately 300-350 cell bodies, and in distinct neuropil regions, neuronal fiber tracts, and varicose endings. Specificity of the immunostaining was tested by preabsorbing the antiserum with FMRFamide, with peptides having similar carboxyl termini to FMRFamide (Met-enkephalin-Arg-Phe, Phe-Met-Arg-Tyr-amide), with several amidated peptides (alpha-melanocyte-stimulating hormone, substance P, oxytocin), and with proctolin, a peptide found widely distributed in the lobster nervous system. Of these substances, only FMRFamide blocked the staining. In addition to the pericardial organs, significant levels of FLI were found in neurosecretory regions associated with thoracic second roots and in the connective tissue sheath that surrounds the ventral nerve cord. In all three regions, immunocytochemical studies showed the FLI to be localized to fine fibers and associated terminal varicosities lying close to the surface of the tissue, with no obvious target in their immediate vicinity. When examined at the ultrastructural level, the immunoreactive varicosities of the thoracic second roots and of the ventral nerve cord sheaths were found a few microns from the surface of the tissue and contained electron-dense granules. In the immunoreactive nerve cord sheath endings, in addition to the large, dense granules, small, clear vesicles were found. The appearance and location of these terminals suggest a neurohormonal role for FMRFamidelike peptides in lobsters. The observation that low levels of FLI are found in the hemolymph supports this suggestion. In addition, the localization of FLI to particular neuronal somata, fiber tracts, and neuropil regions suggests possible functional roles for these peptides in (1) integration of visual and olfactory information, (2) function of the anterior and posterior gut, and (3) the control of exoskeletal muscles.
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PMID:FMRFamidelike peptides of Homarus americanus: distribution, immunocytochemical mapping, and ultrastructural localization in terminal varicosities. 332 67

Calmodulin, a ubiquitous Ca2+-binding regulatory protein, is phosphorylated exclusively on tyrosine-99 in an insulin-dependent manner by wheat germ lectin-purified preparations of insulin receptors from rat adipocyte plasma membranes. Calmodulin is phosphorylated in the presence of polylysine, histone Hf2b, and protamine sulfate, but not in the absence of these cofactors or in the presence of other basic compounds known to interact with calmodulin, such as mellitin, myelin basic protein, chlorpromazine, trifluoperazine, substance P, glucagon, polyarginine, mastoparin, beta-endorphin, spermine, spermidine, and putrescine. The incorporation of 32P into calmodulin, expressed in terms of moles of phosphate per moles of calmodulin and assayed at calmodulin concentrations of 1.2 and 0.06 microM, is 0.023 + 0.002 and 0.046 + 0.006, respectively. This low stoichiometry is likely due to the relative impurity of the receptor preparation, as similar studies not shown here, using highly purified human insulin receptors, yield a stoichiometry of 1 mol phosphate/mol calmodulin. The time course of phosphorylation is characterized by a short initial lag phase of approximately 5 min, a rapid linear rate from approximately 5 to 40 min, with a steady state of 32P incorporation being approached at approximately 60 min. The K0.5 for ATP is 104 + 18 microM. Phosphorylated calmodulin is partially purified by HPLC on a C4 column using a trifluoroacetic acid/acetonitrile gradient solvent system. Phosphoamino acid analysis and limited thrombin digestion were used to determine that the site of insulin-induced phosphorylation of calmodulin is exclusively on tyrosine-99 regardless of the basic protein cofactor used. Phosphorylated calmodulin does not exhibit the characteristic Ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. Thus, the tyrosine phosphorylation of calmodulin represents a potentially important post-translational modification altering calmodulin's ability to regulate a variety of enzymes involved in growth, differentiation, and metabolic regulation.
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PMID:The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. 341 47

The distribution of substance P-like immunoreactivity within the squid retina and brain was studied by immunofluorescence. Positive immunoreactivity was observed as a single layer of fibres in the retina. The retina was devoid of tyrosine-hydroxylase, serotonin, gamma-aminobutyric acid, cholecystokinin, neuropeptide Y, somatostatin, enkephalin and vasoactive intestinal peptide immunoreactivities. Substance P immunoreactivity was particularly abundant in the optic lobe. The optic lobe had a distinct layer of substance P fibres near the periphery. Immunoreactive cell bodies, fibres and varicosities were additionally present in various areas of the optic lobe. Substance P immunoreactivity in the other ganglia of the brain was restricted to a few scattered fibres.
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PMID:Substance P-like immunoreactivity in the retina and optic lobe of the squid. 353 37

The patterns of colocalization of neuropeptides, catecholamines, and catecholamine-synthesizing enzymes were examined in principal neurons and nerve terminals in guinea pig paracervical ganglia using a double-labeling immunohistochemical procedure. A small proportion of nerve cell bodies (less than 10%) had the characteristics of catecholamine-synthesizing neurons and presumably were noradrenergic. Another 50% of the nerve cell bodies contained immunoreactivity (IR) to dopamine-beta-hydroxylase (DBH), but did not have any other characteristics of noradrenergic neurons; they did not contain detectable catecholamines, or IR to dopa decarboxylase (DDC) or tyrosine (TH) hydroxylase, nor did they take up exogenous catecholamines. Half of the catecholamine neurons had neuropeptide Y (NPY)-IR, and a small number (0.5% total neurons) had somatostatin (Som)-IR. Most of the non-noradrenergic neurons with DBH-IR (40-50% total neurons) contained IR for dynorphin (Dyn), NPY, and vasoactive intestinal peptide (VIP), and about half of them (20-25% total) also contained Som-IR. Ten to twenty percent of neurons contained IR to Som, but not to any other antigen examined here. Nerve terminals with substance P (SP)-IR or enkephalin (Enk)-IR were prominent in all ganglia. SP-IR fibers formed dense baskets only around those neurons with DBH/Dyn/NPY/VIP (+/- Som)-IR, while fibers with very bright Enk-IR were associated selectively with those neurons with Som-IR alone. In addition, most TH-IR nerve cell bodies were surrounded by NPY-IR varicose nerve fibers. In conclusion, this analysis of combinations of peptides and enzymes contained in principal neurons of the paracervical ganglia allows us to identify as many as 11 different neuron populations. The functional significance of the presence of the same neuropeptide (e.g., NPY) in different neuron populations is as yet unknown. Some of these classes of neurons are associated specifically with immunohistochemically distinct types of presynaptic nerve fibers, which suggests that different immunohistochemically defined classes of neurons represent different functional pathways.
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PMID:Neuronal colocalization of peptides, catecholamines, and catecholamine-synthesizing enzymes in guinea pig paracervical ganglia. 366 19

The coelomic root of the vagus nerve in goldfish is connected with sensory and motor nuclei of the medulla that are distinct from those serving the orobranchial roots of the same nerve. The primary sensory nucleus for coelomic sensation is itself divisible into medial and lateral subnuclei on the basis of afferent input and immunocytochemistry. The lateral subnucleus receives sensory input from the specialized chewing organ in the posterior pharynx and is poor in both substance P-like and tyrosine-hydroxylase-like immunoreactivities. The medial subnucleus receives input from the subdiaphragmatic gastrointestinal tract and is rich in substance P-like and tyrosine-hydroxylase-like immunoreactivities. The primary sensory fibers that innervate the gastrointestinal tract also project directly to the area postrema and to the vicinity of subdiaphragmatic visceral motor neurons. The vagal motor neuronal pool is divisible into three columns: paramedian (cardiac), medial, and lateral. The paramedian group innervates the heart and is situated in a loosely aggregated column at the boundary zone between the ventricular ependyma and the underlying brainstem. The medial vagal motor neurons innervate the subdiaphragmatic viscera, while the lateral column motor neurons innervate the posterior pharynx and muscles of the chewing organ. The motor neurons in this motor column are arranged in a topographic rostrocaudal order within the motor column according to the muscle of innervation. Thus both the general visceral sensory and general visceral motor nuclei of the medulla are organized into functional domains. Furthermore, in the goldfish, the special visceral (gustatory) and general visceral sensory nuclei form a continuous series in the medulla with the external and oral systems represented anteriorly and the pharyngeal and digestive systems represented posteriorly.
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PMID:Topographic representation of the sensory and motor roots of the vagus nerve in the medulla of goldfish, Carassius auratus. 368 Jun 30

A porcine brain dipeptidyl-aminopeptidase (DAP) has been purified more than 2400-fold from a crude mitochondrial fraction containing synaptosomes. This enzyme catalyzes the release of free Tyr-Gly from Leu-enkephalin (Km = 2.5 microM) with an optimal activity between pH 6.0 and pH 8.0. The enzyme appears homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis devoid of detectable contaminating aminopeptidase activities. The native enzyme is a monomeric protein with a molecular weight of 51,000 +/- 1,000 and an isoelectric point of 4.6 +/- 0.1. This enzyme cosediments with synaptosomes on a Ficoll-sucrose gradient and is partially associated with synaptic plasma membranes. Its activity is inhibited by the metal-chelating agents ethylenediaminetetraacetate and o-phenanthroline. It is not inhibited by the OH-reactive agent phenylmethanesulfonyl fluoride and SH-reactive agents such as p-(chloromercuri)benzoate and N-ethylmaleimide. Among the various biologically active peptides tested, the purified enzyme releases efficiently the N-terminal dipeptide moiety from enkephalins, Trp-Met-Asp-Phe-NH2 (CCK4), and Gly-Trp-Met-Asp-Phe-NH2 (CCK5). At variance, the native peptides CCK8, substance P, neurotensin, and angiotensin II are not cleaved by the DAP. This enzyme is different from other unspecific DAPs, as well as from enkephalin-degrading DAPs previously reported, by its molecular weight and substrate specificity.
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PMID:Purification and characterization of an enkephalin-degrading dipeptidyl-aminopeptidase from porcine brain. 381 77


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