Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cell culture systems were used for studies of neural functions in vitro. A neuronal hybrid cell line (neuroblastoma x glioma hybrid cells) and primary glial-rich cultures of newborn murine brain. The level of cyclic AMP in both systems is regulated by two groups of hormones, those that stimulate and those that inhibit formation of cyclic AMP. Among the inhibitory hormones active on the hybrid cells are opioids. Therefore the cells are being used in the elucidation of action of opioids. The list of stimulating and inhibitory hormones regulating the primary glial-rich cultures includes several peptide hormones such as the gastrointestinal peptides secretin and vasoactive intestinal peptide, the calcaemic hormones parathyrin and calcitonin, adrenocorticotropin and melanotropins, and somatostatin. Noradrenaline (via alpha- and beta-adrenergic receptors) and adenosine (via A1 and A2 receptors) inhibit and stimulate cyclic AMP synthesis in the primary glial-rich cultures. Bradykinin slowly hyperpolarizes the hybrid cells and elicits formation of cyclic GMP. Both responses desensitize rapidly. Substance P increases the permeability of hybrid cells for Na+, as measured by using 14C-guanidinium as substitute for Na+. Hybrid cells actively accumulate taurine, an amino acid that appears to fulfill important functions in the nervous system. The transport of taurine across the plasma membrane is highly specific for and strictly dependent on Na+. The pumped station hypothesis of taurine action in the nervous system views taurine gradient plus taurine carrier as a transport system for the elimination of sodium from neurons during phases of high neuronal activity.
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PMID:Cell culture as models for studying neural functions. 608 74

The effects of substance P, somatostatin, vasoactive intestinal polypeptide, cholecystokinin octapeptide, eledoisin and bombesin on release and metabolism of incorporated (1-14C)-arachidonic acid was investigated in the isolated rabbit ear. The influence of eledoisin and bombesin on release of prostaglandins was compared with that of bradykinin (Sametz and Juan 1982). Only eledoisin and bombesin stimulated the release of prostaglandins I2 and E2 but with a lesser potency than bradykinin. Only eledoisin in a high dose stimulated nociceptors per se whereas bombesin did not. Eledoisin and bombesin in a low dose enhanced nocicpetion induced by acetylcholine in the rabbit ear; this enhancement of the algesic effect of acetylcholine was abolished by indometacin which indicates a sensitization of nociceptors by released prostaglandins. Although effects of eledoisin and bombesin are mediated at least in part by released prostaglandins, the nociceptor-stimulating and prostaglandin-releasing potency of bradykinin remaines unique among all peptides tested so far.
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PMID:Prostaglandin release and nociceptor stimulation by peptides. 608 99

A group of 15 biologically active peptides were studied with respect to their susceptibility to chain shortening by human pancreas alanine aminopeptidase. Those susceptible were somatostatin, melanocyte stimulating hormone, fibrinopeptide A, eosinophilotactictetrapeptide, lysyl-bradykinin, and methionyl-lysyl-bradykinin. The latter two were selected for further study. Direct identification and determination of the reaction products, lysine and/or methionine, were undertaken to establish unequivocally the kinin-converting activity of human pancreas alanine aminopeptidase, which exhibited a pH optimum at pH 7.9. The Km and kcat values for this enzyme for lysyl-bradykinin were 57 mumol/l and 3000 min-1, respectively. The corresponding values for this enzyme for methionyl-lysyl-bradykinin were calculated to be 49 mumol/l and 16000 min-1, respectively. Bradykinin itself is extremely resistant to hydrolysis by this pancreatic enzyme.
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PMID:Action of human pancreas alanine aminopeptidase on biologically active peptides: kinin converting activity. 611 80

In order to study the secretory mechanism of human placental lactogen (hPL:hCS) from trophoblastic tissues, tissue culture and new placental perifusion systems were developed and used to clarify the effect of various substances on the secretion of hPL. These substances were (1), metal ions([Ca2+], [K+], [mg2+], [Na+]); (2) growth hormone and prolactin releasing or inhibiting factors (arginine, TRH, somatostatin, dopamine); (3) LH-RH, dibutyryl cyclic-AMP which stimulates hCG secretion; (4) prostaglandins F2 alpha and E2, bradykinin; (5) EGF and insulin which have the receptors in the placenta; (6) glucose. It was found that most of the substances examined had no effect on the secretion of hPL, except dopamine and glucose. The effect of dopamine in the tissue culture system is dose-dependent. At high concentrations dopamine slightly inhibited hPL secretion(5mM: 38.6 +/- 15.0 and 10mM; 35.7 +/- 19.0 micrograms/g wet tissue) compared with the control (63.2 +/- 29.8 microgram/g wet tissue). However, these effects may be due to the deviation of pH in the medium from the direct addition of dopamine hydrochloride. At a low concentration(1mM) it was observed to have a rather stimulatory effect (125.7 +/- 18.0 micrograms/g wet tissue, p less than 0.05), but in the perifusion system, this effect could not be observed. The addition of glucose in the perifusion system gave a slightly higher hPL secretion than that of the control. Perhaps this resulted from increased cell activity rather than a stimulatory effect. an incorporation experiment of [3H] leucine was also carried out to study the biosynthesis of hPL. Newly synthesized ([3H]-labelled) hPL was secreted into the medium within two hours. Furthermore, a labelled larger molecular weight substance together with the tritiated hPL was also observed on a Sephadex G-100 gel chromatography. These labelled substances were immunoprecipitable using an anti-hPL serum, indicating that the substances contain the same immunological determinants. This result indicates that the larger molecular substance may represent the biosynthetic precursor or the aggregate of hPL. These data indicate that the secretion of hPL has a unique mechanism, different from GH and PRL, and may be self regulated.
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PMID:[Studies on the secretion of human placental lactogen from human trophoblastic tissues (author's transl)]. 612 18

Determining the relationships between conformation and biological activity in peptide hormones and neurotransmitters is an important goal of contemporary biology. A major difficulty in these studies is the conformational flexibility of most peptides and the high dependence of the conformations on environment. The question arises whether conformations determined in solution are relevant to those important to the peptide at the membrane receptor(s). One recent approach to overcome these difficulties has been the use of conformational constraints by covalent bonding of side chain groups of residues in the peptide. In this manner linear peptides are rendered cyclic, and cyclic peptides are further conformationally constrained either by ring contractions or by other conformational constraints. Biologically active peptides specifically designed by this approach have been found to possess several useful properties including: 1) greater conformational integrity; 2) increased agonist or antagonist potency; 3) prolonged biological activity; 4) increased enzymatic stability; and 5) increased specificity for a particular receptor. Careful applications of this approach have provided important new designs features for peptide structure-function studies, and new insights into peptide conformation-activity relationships for oxytocin, somatostatin, enkephalin, bradykinin, vasopressin, and other biologically active peptides.
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PMID:Conformational restrictions of biologically active peptides via amino acid side chain groups. 612 94

We have previously shown that stimulation of the preganglionic cervical sympathetic trunk leads to an acute increase in tyrosine hydroxylase (TyrOHase) activity in the rat superior cervical ganglion. This increase appears to be mediated in part by acetylcholine and in part by a second neurotransmitter. As a first step in an attempt to determine the identity of this noncholinergic transmitter, we have examined the ability of a number of neuropeptides to increase ganglionic TyrOHase activity in vitro. Secretin and vasoactive intestinal peptide (VIP) both stimulated TyrOHase activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, glucagon, insulin, luteinizing hormone-releasing hormone, [D-Ala(2), Met(5)]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin produced a significant increase in TyrOHase activity at 1 nM and a maximal elevation at 0.1 muM. VIP produced a significant increase at 0.1 muM and a near maximal effect at 10 muM. Although secretin was about 2 orders of magnitude more potent than VIP, it produced a significantly smaller maximal increase in enzyme activity. Incubation of ganglia with both secretin (10 muM) and VIP (10 muM) produced an increase in TyrOHase activity that was not significantly different from that produced by VIP alone. The stimulatory effects of secretin and VIP were reversible within minutes after removal of the peptides. Neither incubation of intact ganglia with the cholinergic antagonists hexamethonium and atropine nor prior decentralization of ganglia altered the response to the peptides. Thus, the data demonstrate that secretin and VIP acutely increase TyrOHase activity in the superior cervical ganglion and suggest that they produce this effect by acting directly on ganglionic neurons. It remains to be determined whether secretin or VIP or a related peptide is released during preganglionic nerve firing and whether one or more of these peptides is responsible for the noncholinergic elevation of TyrOHase activity produced by preganglionic nerve stimulation.
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PMID:Secretin and vasoactive intestinal peptide acutely increase tyrosine 3-monooxygenase in the rat superior cervical ganglion. 613 May 26

Nanomolar concentrations of neurotensin caused a dose-dependent contraction of the longitudinal muscle layer of the guinea-pig ileum. The contractile activity of neurotensin was partially blocked by tetrodotoxin or atropine, indicating that a component of the neurotensin-mediated contraction is indirect in nature and likely involves the release of endogenous acetylcholine from nervous terminals in the myenteric plexus. Dynorphin and related peptide fragments also blocked in part the neurotensin contraction; the potency of this opioid peptide was about the same as that of atropine. Other peptides and alkaloids tested for ability to block the neurotensin contractures included the enkephalins, beta-endorphin, normorphine and the ketocyclazocines; all these opioids inhibited in a dose-dependent fashion the neuronal component of the excitatory effect of neurotensin. The potency of these compounds to reduce the contractions of neurotensin showed good correlation with the potency of these agents to depress by 50% the electrically evoked neuromuscular twitches in the same tissue (r = 0.99); in these tests dynorphin was found to be the most potent of the endogenous opioid-like peptides. The dynorphin blockade was selective to the excitatory effect of neurotensin because the opioid peptide did not antagonize the contractile action of acetylcholine, histamine, substance P, angiotensin II, bradykinin, Ba++ or K+ ions. In addition, somatostatin, vasointestinal peptide, gastrin or adenosine did not modify the potency of neurotensin whereas thyrotropin releasing hormone and epinephrine caused a modest doubling of the neurotensin EC50. The inhibitory action of dynorphin was reduced in the presence of naloxone, suggesting that the interaction involved opiate receptors. Morphine tolerance was not extended to the inhibitory action of dynorphin as evidenced by the finding that the potency of dynorphin-(1-13) to block the neurotensin responses was increased after chronic morphine exposure. In contrast, the potency of dynorphin-(1-13) was significantly reduced in tissues rendered tolerant to the action of ketocyclazocine or ethylketocyclazocine, suggesting that the action of dynorphin could be partially mediated via occupation of K-opiate receptors. Thus, a cholinergic-neuronal component activated by neurotensin on the myenteric plexus appears to be under the inhibitory influence of opiate receptors, suggesting that dynorphin may play a role in the modulation of cholinergic synapses on the enteric nervous system.
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PMID:Dynorphin inhibition of the neurotensin contractile activity on the myenteric plexus. 614 Dec 81

Electrical field stimulation of the isolated pig bladder neck preparation initiated rapid non-adrenergic, non-cholinergic nerve-mediated relaxations. A wide range of substances were examined as possible candidates for the neurotransmitter involved. Of these, only 5-hydroxytryptamine, vasoactive intestinal polypeptide, adenosine and adenosine 5'-triphosphate produced relaxations. Noradrenaline, acetylcholine, substance P, bradykinin and angiotensin II caused contraction, while neurotensin, somatostatin, bombesin and gamma-amino butyric acid were without effect. The nerve response was not blocked by methysergide, ketanserin, chymotrypsin, apamin or 8-phenyltheophylline, although methysergide antagonised the responses to 5-hydroxytryptamine, chymotrypsin blocked the responses to VIP, and 8-phenyltheophylline antagonised the responses to adenosine and ATP.
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PMID:A novel non-adrenergic, non-cholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. 614 1

We have examined the ability of a number of neuropeptides to increase tyrosine hydroxylase (TH) activity in the superior cervical ganglion in vitro. Secretin and vasoactive intestinal peptide (VIP) both increased TH activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, insulin, luteinizing hormone-releasing hormone, [D-Ala2, Met5]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin and VIP increased TH activity with an EC50 of 5 nM and 0.5 microM, respectively. The effects of these peptides were not altered by prior decentralization of the ganglia, by addition of hexamethonium (3 mM) and atropine (6 microM), or by lowering the concentration of calcium in the medium to 0.1 mM. Addition of carbachol (3 microM) potentiated the effects of both secretin and VIP on TH activity. Several gastrointestinal peptides with structural similarities to secretin and VIP were examined for their ability to increase TH activity. Glucagon, gastric inhibitory peptide and human pancreatic tumor growth hormone-releasing factor produced no effect at a concentration of 10 microM, while PHI increased enzyme activity.
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PMID:Acute stimulation of ganglionic tyrosine hydroxylase activity by secretin, VIP and PHI. 614 16

Acute intracerebral injection of the undecapeptide, substance P, in mice induced a unique reciprocal hindlimb scratching response whose intensity was dose-related. Similar intracerebral dose-response curves were obtained by the structurally related undecapeptides, physalaemin and eledoisin, but not by several unrelated peptides (TRH, neurotensin, bradykinin, somatostatin), prostaglandins E2 and F2a, dibutyryl cyclic AMP or dibutyrylcyclic GMP. Analgesic narcotic agents with predominant agonist activity administered i.p. prevented the reciprocal hindlimb scratching response induced by intracerebral substance P (0.625 microgram/mouse = ED 95). In this in vivo assay their action was stereospecific and exhibited a rank order of potency similar to that reported for analgesic activity and binding to opiate receptors in vitro. Narcotic agents with mixed agonist-antagonist activity were inactive while the narcotic antagonist, naloxone, completely reversed the action of morphine. Higher doses of naloxone alone potentiated substance P-induced reciprocal hindlimb scratching which may explain why partial narcotic agonists failed to abolish the response. There is now considerable evidence in support of a sensory neurotransmitter/modulator role for substance P within the central nervous system, and one of its actions may be associated with nociception. This concept is supported by observations in the present study which indicate that the substance P-induced reciprocal hindlimb scratching response involves nociceptive pathways within the central nervous system.
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PMID:Intracerebral substance P in mice: behavioral effects and narcotic agents. 616 31


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