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

The pathophysiological role of endorphins in septic shock was studied in a porcine model. Septic shock was induced by the intravenous infusion of live Escherichia coli. Naloxone hydrochloride, an opiate receptor blocker, given during profound septic shock, increased blood concentrations of glucagon and cyclic adenosine monophosphate (cAMP), while BP and cardiac output increased transiently. Heart rate and hepatic glycogen value decreased, but insulin and cortisol levels remained unchanged. In contrast, exogenous morphine injection produced further reduction of BP, increased pulmonary wedge pressure, and increased substance P, while growth hormone level and cardiac output remained unchanged. Neither hormonal nor hemodynamic changes were noted in saline controls. Thus, the endogenous opiates appear partly responsible for the hemodynamic derangements during septic shock, and naloxone is able to reverse such depression, even though the effects are transient and relatively minor when naloxone is given late in the course of septic shock. Endogenous opiates also affect the hormonal homeostasis in shock, and there are indications that this may be mediated by the adenylate cyclase-cAMP system.
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PMID:Endorphins in septic shock: hemodynamic and endocrine effects of an opiate receptor antagonist and agonist. 628 53

Numerous biologically active peptides are present in normal lung. Some of these, like vasoactive intestinal peptide (VIP) and substance P, are neuropeptides that may function as neurotransmitters or neuromodulators. The activities of lung peptides include relaxation or contraction of airway and pulmonary vascular smooth muscle, modification of bronchial water and mucus secretion, and stimulation of adenylate cyclase activity. Much remains to be learned about active peptides in the lung: their full identities, their localization, their physiologic roles, and their participation in disease processes. One of these peptides, VIP, widely distributed in other organ systems, may mediate the nonadrenergic relaxation of airways and pulmonary vessels. It may also regulate bronchial secretion and, through its promotion of cyclic adenosine monophosphate accumulation in the lung, may modulate the immunologic release of mediators from mast cells.
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PMID:Vasoactive peptides in the lung, with special reference to vasoactive intestinal peptide. 676 62

Adenylate cyclase was stimulated by prostaglandin E2 (PGE2) and parathyroid hormone-related protein (PTHrP) in both these types of fibroblast and by calcitonin gene-related protein (CGRP) in the human fibroblasts in vitro. PGE2 (1 microM), CGRP (1 microM), and PTHrP (1 microM) stimulated adenylate cyclase up to 50-fold, 10-fold and 9-fold, respectively. Calcitonin (CT), substance P (SP), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF beta 1) had no effect on adenylate cyclase in either fibroblast. Intracellular Ca2+ (iCa2+) was measured in individual fibroblasts from the periodontal ligament using Indo-1 and an adherent cell analysis and sorting interactive laser cytometer. Ionomycin (3 microM) caused a transient rise of iCa2+ in all human and canine fibroblasts tested. The mean percentage increase in iCa2+ in response to ionomycin was 820 and 840% for human and canine fibroblasts, respectively. The human fibroblasts responded to PGE2 (1 microM) by an increased iCa2+ concentration; the mean percentage increase in iCa2+ was 187%. SP caused a less pronounced increase in iCa2+ in the human fibroblasts (56%). CGRP and SP caused a similar response in the canine fibroblasts. The mean percentage increase in iCa2+ in response to SP and CGRP was 95 and 78%, respectively. PTH, PTHrP, platelet-activating factor, CT, and IL-1 beta had no effect on iCa2+ in either type of fibroblast. The data indicate that cAMP and calcium have roles as intracellular secondary messengers in the action of PGE2, SP, CGRP, and PTHrP in fibroblasts of human and canine periodontal ligament.
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PMID:Effects of hormones and cytokines on stimulation of adenylate cyclase and intracellular calcium concentration in human and canine periodontal-ligament fibroblasts. 750 23

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide-like hypothalamic peptide occurring as two variants, PACAP-27 and the C-terminally extended PACAP-38. Immunoreactive PACAP has also been demonstrated in the enteric nervous system and in the innervation of the respiratory tract. We have examined the possibility that PACAP occurs in the sensory nervous system of the rat. Immunocytochemistry revealed PACAP in numerous nerve fibres in the superficial layer of the dorsal horns of the spinal cord, in nerve cell bodies (most of them of small size) of the spinal ganglia and trigeminal ganglia and in nerve fibres running close to and within the surface epithelium in the skin of the nose, the tongue, the larynx-trachea, and the urinary bladder as well as around the ducts of the submandibular gland. In all locations, PACAP co-existed with calcitonin gene-related peptide and substance P, the PACAP-immunoreactive fibres and cell bodies constituting a subpopulation of those storing substance P and/or calcitonin gene-related peptide. Additional PACAP-immunoreactive fibres not associated with epithelia seemed to lack calcitonin gene-related peptide and substance P. Capsaicin treatment reduced the density of PACAP- and calcitonin gene-related peptide/substance P-immunoreactive fibres in the tissues examined. On the whole, the immunocytochemical results agreed with those obtained by radioimmunoassay for PACAP and CGRP. The data favour a role for PACAP in primary sensory neurons.
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PMID:Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. 750 77

Several neuropeptides, calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), vasoactive intestinal polypeptide (VIP), the noradrenergic marker dopamine beta-hydroxylase (DBH) and the general neuroendocrine marker PGP 9.5 were localized by immunocytochemistry in the parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep. The general density of innervation varied markedly among the species. Nerve fibers storing CGRP, NPY, PACAP, SP and VIP were present in all species examined. Galanin-containing fibers occurred in all species except guinea-pig and adrenergic (DBH-containing) fibers in all species except chicken and guinea-pig. Generally, the nerve fibers were distributed around blood vessels, in the parenchyma as single scattered fibers, and often also within the capsule. Coexistence studies were performed in cat and sheep. CGRP and SP invariably coexisted in the same nerve fibers. Further, CGRP partially coexisted with PACAP, NPY was observed in the same nerve fibers as DBH. A small population of NPY-containing fibers also seemed to contain galanin (cat only). VIP and NPY coexisted in a population of nerve fibers in the parenchyma. A population of VIP-containing fibers also seemed to contain PACAP. The results indicate the presence of several neuropeptides in the parathyroid glands. As judged by their distribution patterns they may regulate both secretory activity and blood flow, some of them possibly in a cooperative manner.
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PMID:Peptide-containing nerve fibers in the parathyroid glands of different species. 751 98

The human c-kit receptor ligand, rhSCF, is the only cytokine known to be active on human mast cells, but its intracellular signal transduction pathway is still unknown. We compared the effect of rhSCF on intracellular Ca2+ levels in purified (> 70% pure) adult skin mast cells with two other immunologic stimuli, namely, anti-IgE and substance P. Both rhSCF (1 microgram/mL) and anti-IgE (3 micrograms/mL) induced a rapid (< 20 sec) and sustained (T1/2 for decay > 10 min) increase in free cytosolic Ca2+ concentration. In contrast, substance P (5 microM) elicited a very rapid (< 1 sec) and transient (T1/2 for decay congruent to 5 sec) rise in intracellular Ca2+ levels. Intracellular cAMP levels were then increased by pharmacologic means to examine the role of the cyclic nucleotide in controlling the Ca2+ response in skin mast cells. A combination of the general phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX) (200 microM) and the adenylate cyclase activator, forskolin (30 microM) was effective in inhibiting the Ca2+ response induced by rhSCF or anti-IgE (82 and 68% inhibition, respectively), while IBMX and forskolin alone were much less effective. The phosphodiesterase isozyme IV inhibitor, rolipram (10 microM), variably affected the increase in Ca2+ levels induced by anti-IgE, but it exerted a significant inhibitory activity on anti-IgE- or rhSCF-induced response in the presence of forskolin (30 micrograms/mL) (33 and 67%, respectively). Two different protein kinase C (PKC) activators TPA (200 nM) and bryostatin 1 (200 nM) similarly inhibited rhSCF- (22 and 32%, respectively) and anti-IgE-induced (24 and 32%) Ca2+ response. Finally, the kinase inhibitor genistein (30 micrograms/mL) was a somewhat more effective inhibitor of the rise in intracellular Ca2+ induced by rhSCF (100%) than that activated by anti-IgE (54%) (P < 0.05). These data indicate that rhSCF and anti-IgE may act on human mast cells through a common pathway to increase free cytosolic Ca2+ levels and this effect is similarly modulated by various drugs.
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PMID:Studies of the intracellular Ca2+ levels in human adult skin mast cells activated by the ligand for the human c-kit receptor and anti-IgE. 751 34

Intracellular signaling by an increase in [Ca2+]i was observed in pancreatic AR42J cells in response to agonists whose receptors are G-protein coupled including cholecystokinin (CCK), bombesin, carbachol, substance P, pituitary adenylate cyclase activating peptide (PACAP), bradykinin, ATP, calcitonin gene related peptide (CGRP), and in response to growth factors EGF and FGF whose receptors are tyrosine kinases. The response to growth factors was smaller both in magnitude and in the percentage of cells responding but was independent of extracellular Ca2+. CCK and carbachol induced sizeable increases in inositol phosphates while growth factors did not. The responses to both carbachol and EGF, however, were blocked by the phospholipase C inhibitor U73122. The tyrosine kinase inhibitor, genestein, blocked the response to EGF but not that to CCK. These data are consistent with two types of signaling mechanisms in AR42J cells. Secretagogues act on receptors which couple through G proteins to induce a large amount of inositol phosphate production and subsequent intracellular Ca2+ mobilization. Growth factors act on receptors which signal through tyrosine kinase activity and in this cell type produced limited amounts of inositol phosphate and a smaller increase in intracellular Ca2+.
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PMID:Ca2+ signaling through secretagogue and growth factor receptors on pancreatic AR42J cells. 753 85

There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.
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PMID:Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas. 758 83

To elucidate the regulation mechanism of adrenomedullin (AM) production in blood vessels, we examined the effects of 30 substances on AM production in cultured rat vascular smooth muscle cells (VSMCs). Forskolin and 8-bromo-cAMP suppressed production and gene transcription of AM. Since VSMC expresses AM receptors coupled with adenylate cyclase, AM production may be regulated by intracellular cAMP concentration. Thrombin, vasoactive intestinal polypeptide and interferon-gamma also inhibited AM production, while angiotensin II, endothelin-1, bradykinin, substance P, adrenaline, phorbol ester and fetal calf serum stimulated AM production in VSMC. These results suggest that AM production is regulated by a variety of substances, indicating complex systems regulating AM production.
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PMID:Effects of vasoactive substances and cAMP related compounds on adrenomedullin production in cultured vascular smooth muscle cells. 764 78

Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs alpha protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres. Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP [CGRP-(8-37)] that is a specific competitive inhibitor of CGRP. Substance P and calcitonin failed to induce cAMP in LC. Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP. The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC line, whereas calcitonin did not. CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event. However, the induction of cAMP by itself does not account for inhibition of antigen presentation. Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation.
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PMID:Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects. 766 88


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