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)

A peptide derived from fibrinogen degraded by leukocyte elastase, and corresponding to amino acids 30-43 in the B beta-chain of fibrinogen, was evaluated concerning its effects on isolated bovine mesenteric arteries. This peptide induced dilation of the arteries and an increase in both cyclic AMP and cyclic GMP in the vessels. In addition there was an increase in 6-keto-PGF1 alpha indicating an increased release of prostacyclin. The increase in cyclic nucleotides and 6-keto-PGF1 alpha was inhibited by indomethacin, as was the vasodilation. The increase in cyclic GMP was much larger than the increase in cyclic AMP. The effects of the studied peptide are similar to the effects of other vasoactive peptides with a similar structure, such as bradykinin, neurotensin and substance P. The increase in cyclic AMP is probably caused by prostacyclin, a probable mediator of vasodilation. In addition, in certain species vasodilation may be caused by an increase in cyclic GMP.
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PMID:Effect of a peptide derived from fibrinogen degraded by leukocyte elastase on isolated bovine mesenteric arteries. 254 16

It is well established now that activation of Ca2+ -mobilizing receptors results in the phosphodiesteratic breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2), instead of phosphatidylinositol (PI), into myoinositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG). There is also accumulating experimental evidence which indicates that IP3 and DG may function as second messengers, the former to mobilize Ca2+ from intracellular sites and the latter to activate protein kinase C (PKC). In this review, I have recounted our early studies, which began in 1975 with the original observation that activation of muscarinic cholinergic and adrenergic receptors in the rabbit iris smooth muscle leads to the breakdown of PIP2, instead of PI, and culminated in 1979 in the discovery that the stimulated hydrolysis of PIP2 results in the release of IP3 and DG and that this PIP2 breakdown is involved in the mechanism of smooth muscle contraction. In addition, I have summarized more recent work on the effects of carbachol, norepinephrine, substance P, the platelet-activating factor, prostaglandins, and isoproterenol on PIP2 hydrolysis, IP3 accumulation, DG formation, myosin light chain (MLC) phosphorylation, cyclic AMP production, arachidonic acid release (AA) and muscle contraction in the iris sphincter muscle. These studies suggest: (a) that the IP3-Ca2+ signalling system, through the Ca2+ -dependent MLC phosphorylation pathway, is probably the primary determinant of the phasic component of the contractile response; (b) that the DG-PKC pathway may not be directly involved in the tonic component of muscle contraction, but may play a role in the regulation of IP3 generation; (c) that there are biochemical and functional interactions between the IP3-Ca2+ and the cAMP second messenger systems, cAMP may act as regulator of muscle responses to agonists that exert their action through the IP3-Ca2+ system; and (d) that enhanced PIP2 turnover is involved in desensitization and sensitization of alpha 1-adrenergic- and muscarinic cholinergic-mediated contractions of the dilator and sphincter muscles of the iris, respectively. The contractile response is a typical Ca2+ -dependent process, which makes smooth muscle an ideal tissue to investigate the second messenger functions of IP3 and DG and their interactions with the cAMP system.
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PMID:Calcium-mobilizing receptors, polyphosphoinositides, generation of second messengers and contraction in the mammalian iris smooth muscle: historical perspectives and current status. 254 19

The relationship between glucose metabolism and cyclic-AMP production in dental pulp in the presence of chemical mediators was investigated in vitro. It is generally accepted that oxidation of glucose-6-14C is indicative of metabolism by the glycolytic pathway whereas that of glucose-1-14C occurs by the hexose monophosphate shunt. The 14CO2 productions from both routes were compared in dental pulp from cattle and rats in the presence of each of several chemical mediators: bradykinin (1.7-3.3 micrograms/ml), prostaglandin E1 (0.3 micrograms/ml), prostaglandin E2 (0.3 micrograms/ml), histamine (33 micrograms/ml), and 5-hydroxytryptamine (33 micrograms/ml). The effects of dental filling materials on glucose oxidation, and cyclic-AMP production by chemical mediators in pulp tissues were also investigated. The results obtained were as follows: 1) Glucose oxidation in dental pulp was stimulated by chemical mediators generally by way of the Embden-Meyerhof Parnas pathway, and was further stimulated by the medium containing bradykinin. However, it was depressed in the presence of higher concentrations of chemical mediators, especially depressed in the HMS pathway. 2) The oxidation ratio of glucose-1-14C to glucose-6-14C (G1/G6) in dental pulp was 4 to 8 in the cattle and 0.6 in the rat, showing clear differences in glucose oxidation between the two animals. 3) Moreover, glucose oxidation in rat dental pulp was 60 to 80 times higher in the EMP pathway and 5 to 10 times higher in the HMS pathway than those in the cattle. 4) Dental filling materials such as silicate cement, zinc phosphate cement, calcium hydroxide, and eugenol cement severely depressed glucose-6-14C oxidation in bovine dental pulp when used at high concentrations, but not at low concentrations. 5) The chemical mediators tested in this experiment (PGE1, PGE2, histamine, 5-HT, bradykinin, and substance P) stimulated cyclic AMP production in rat dental pulp. The production was highest with PGE1 and PGE2. The cyclic AMP production was further stimulated by addition of histamine or 5-HT to the medium containing PGE1 or PGE2.
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PMID:[Studies on the relation between glucose metabolism and c-AMP formation in dental pulps in the presence of inflammatory chemical mediators in vitro]. 256 77

The mammalian tachykinins substance K, neuromedin K and substance P stimulated inositol phospholipid hydrolysis in paired coronal sections through the rat brain. In contrast, none of these peptides had any effect on either basal or forskolin-stimulated cyclic AMP levels. The present results therefore implicate inositol phospholipid hydrolysis as a possible second messenger system mediating the effects of substance K and neuromedin K in addition to substance P.
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PMID:Mammalian tachykinin-induced hydrolysis of inositol phospholipids in rat brain slices. 257 57

Explants and cell cultures of embryonic chick ganglia trigeminalia, telencephalon and retina or hippocampus from fetal rats were incubated in maximow chambers in the presence of cyclic AMP and the dipeptide cyclo(Lys-Pro).HCL under various conditions. Maintenance of nerve cells and growth of nerve fibers were observed by morphometrical methods. 1. Cyclo(Lys-Pro).HCL promoted the maintenance of neuroblasts and the growth of nerve fibres in explants of the ganglion trigeminal and retinal cell cultures. The effect depended on the presence of serum in the medium by use of poly-I-lysine substrate. 2. Extern applicated cyclic AMP and the dipeptide SP3-4 = cyclo(Lys-Pro).HCL facilitated neurite growth in PNS cultures. In the presence of the drugs the length of nerve fibers increased for a short term. On CNS explants substance P (SP1-11) and SP3-4 were without effect. Cyclic AMP stimulated the growth of nerve fibers in CNS explants and cell cultures in number and length. 3. Discussed is the effect of SP1-11 and cyclo(Lys-Pro).HCL for competence of nerve fibre regeneration in vitro in relation to increasing cAMP levels, which may then act as an initial second messenger. It is suggested that explants and cell cultures of nervous tissues will be useful as a tool for the further characterisation of factors with neuronotrophic activities.
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PMID:[Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture]. 282 94

We studied the effects of neurokinin A (NKA) and neurokinin B (NKB), the mammalian-derived tachykinins, on the electrical and ion transport properties of canine tracheal epithelium. Both tachykinins dose-dependently increased short-circuit current (Isc) when added to the mucosal (NKA: delta Isc(max) = 24.2 +/- 2.4 microA/cm2, KD = 9 nM; NKB: delta Isc(max) = 1.42 +/- 2.2 microA/cm2, KD = 32 nM) or submucosal (NKA: delta Isc(max) = 10.5 +/- 1.2 microA/cm2, KD = 45 nM; NKB: delta Isc(max) = 2.2 +/- 1.4 microA/cm2, KD = 80 nM) bath. Isc responses to mucosal addition of tachykinins consisted of transient and subsequent steady-state components, whereas submucosal addition elicited only steady-state responses. Inhibition of Cl transport with bumetanide or substitution of Cl reduced the maximal changes in Isc. In paired tissues, NKA increased net 36Cl flux toward the mucosa from 1.83 +/- 0.49 to 2.71 +/- 0.46 mu eq.cm-2.h-1 (p less than 0.05), without affecting net 22Na flux toward the submucosa. The increases in Isc induced by tachykinins were not modified by prior tissue incubation with phentolamine, propranolol, atropine, tetrodotoxin, or indomethacin, but were effectively inhibited by (D-Pro2, D-Trp7,9)substance P. The cyclic AMP (cAMP) levels in the surface epithelium were increased by the addition of NKA and NKB. These findings suggest that NKA and NKB selectively stimulate the secretion of Cl across canine tracheal epithelium, probably by acting directly on the tachykinin receptors, and that these effects are associated with the increased production of intracellular cAMP.
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PMID:Stimulation of Cl secretion by neurokinin A and neurokinin B in canine tracheal epithelium. 283 41

The neuropeptide vasoactive intestinal peptide (VIP) has been shown to stimulate cyclic AMP accumulation in Leydig cells isolated from rat testis. The effect was dependent on time, temperature and cell concentration. At 15 degrees C, half-maximal and maximal stimulation were observed at about 1 and 100 nM VIP, respectively. The interaction was specific since an order of potencies chicken VIP greater than rat VIP greater than secretin greater than glucagon and no effect of neurotensin and substance P were obtained. The efficiency of VIP was lower in pubertal rats and then increased in young-adult and adult animals. These results together with the known presence of VIP in the testis support the idea that VIP may be involved in the regulation and function of Leydig cells during development.
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PMID:Characterization and age dependence of the stimulatory effect of VIP on cyclic AMP accumulation in rat Leydig cells. 283 54

We investigated the role of neuropeptides and adrenergic agonists in the regulation of intracellular 3',5'-cyclic adenosine monophosphate (cyclic AMP) contents in cultured Schwann cells from sciatic nerve of neonatal Sprague-Dawley rats. Of the neuropeptides examined, vasoactive intestinal polypeptide (VIP) and secretin markedly stimulated the accumulation of intracellular cyclic AMP in a time- and dose-dependent manner with half maximum at 3 and 12 min, and 2.8 X 10(-5) and 5.0 X 10(-5) M, respectively. While somatostatin, substance P, adrenocorticotropin (ACTH), beta-endorphin, and nerve growth factor (NGF) did not show any effect on cyclic AMP metabolism, isoproterenol (IP), norepinephrine (NE) and epinephrine (E) also markedly elevated the Schwann cell cyclic AMP concentration. The rank-order of potency of these adrenergic catecholamines on cyclic AMP accumulation was isoproterenol greater than norepinephrine greater than epinephrine. Simultaneous addition of VIP or secretin to the Schwann cell culture synergistically enhanced the norepinephrine-induced elevation of intracellular cyclic AMP. The effect of norepinephrine was antagonized by a selective beta 1-adrenergic antagonist but not by beta 2- nor alpha-adrenergic antagonists. These results suggest that VIP, secretin, and beta 1-adrenergic agonists alone or synergistically may play a part in the regulation of metabolism of Schwann cells mediated through a cyclic AMP-dependent mechanism.
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PMID:Peptidergic and adrenergic regulation of the intracellular 3',5'-cyclic adenosine monophosphate content in cultured rat Schwann cells. 285 16

The results of our investigations into the localization of Na+,K+-pump activity in pancreatic and parotid acinar cells and the effects of hormones and neurotransmitters on pump turnover can be integrated with data on other aspects of stimulus-response coupling to construct models of the neurohumoral control of protein, fluid, and electrolyte secretion (Fig. 23). In both tissues, Ca2+ and cyclic AMP serve as intracellular messengers. In pancreatic acinar cells, the Ca2+-dependent pathway activated by the occupation of CCK or cholinergic receptors provides the primary stimulus for digestive enzyme secretion. Cyclic AMP plays a comparatively minor role; VIP and secretin are much less effective stimulators of protein secretion. Conversely, cyclic AMP levels in parotid acinar cells, which are modulated primarily through occupation of beta-adrenergic receptors, are a major determinant of enzyme secretion. Activation of the Ca2+-dependent pathway by cholinergic or alpha-adrenergic agonists or substance P is less important. The presence of dual control processes in each gland suggests that the observed differences in effectiveness of cyclic AMP- versus Ca2+-dependent secretagogues may reflect not different mechanisms, but rather a shift in the relative emphasis placed on each pathway. This emphasis could conceivably result from subtle variations in the interaction between cellular protein kinases and phosphatases and their phosphoprotein substrates. Electrolyte secretion, on the other hand, appears to involve both discrete and common entities. In pancreatic acinar cells from rodent species, cholinergic or CCK receptor occupancy elicits a Ca2+-dependent increase in the open-state probability of nonselective cation channels in the basolateral plasma membrane. The resultant influx of Na+ and efflux of K+ is most probably the factor which activates Na+, K+-pumps. Based on electron probe studies of the effects of cholinergic agonists on acinar cell Na+ and K+ contents discussed earlier, a transient reduction in the intracellular K+/Na+ ratio of up to 4-fold may occur. A shift of this magnitude in the cytoplasmic microenvironment of the Na+, K+-pump clearly would have a stimulatory influence (see discussion by Jorgensen, 1980). In addition, Ca2+ itself may have direct effects on Na+,K+-pump activity. Calcium at levels much above 1 microM progressively inhibits Na+,K+-ATPase activity (Tobin et al., 1973; Yingst and Polasek, 1985). In unstimulated guinea pig pancreatic acinar cells, Ca2+i measured by quin-2 fluorescence was 161 +/- 13 nM (Hootman et al., 1985a) which increased to a maximal concentration of 803 +/- 122 nM following CCh stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroendocrine control of secretion in pancreatic and parotid gland acini and the role of Na+,K+-ATPase activity. 287 3

It has recently been demonstrated that several neuropeptides can affect cell growth. The mammalian tachykinins substance P and neurokinin A, which are present in peripheral sensory neurons, stimulate growth of cultured connective tissue cells. Substance P-like immunoreactivity has been demonstrated in neuroblastoma cell lines. Neuroblastoma cells also produce other neuropeptides, among them vasoactive intestinal polypeptide (VIP). We report here that VIP is a potent inhibitor of serum-induced DNA synthesis in cultured smooth muscle cells (SMC), whereas no growth-inhibition was seen in SMC exposed to neurokinin A, calcitonin-gene related peptide, neuropeptide Y, somatostatin, or cholecystokinin. The growth-inhibitory effect of VIP was closely related to its ability to induce formation of cyclic AMP. Our results raise the possibility that peptides released by neurons, endocrine cells, as well as by transformed cells, may not only function as mitogens but also as inhibitory modulators of cell growth.
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PMID:Growth-inhibitory properties of vasoactive intestinal polypeptide. 290 57


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