Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin acts within the brain to produce a prompt and sustained hyperglycemia, hyperglucagonemia, and relative or absolute hypoinsulinemia. Bombesin does not decrease plasma glucose turnover. Acute adrenalectomy but not hypophysectomy prevents hyperglycemia and hyperglucagonemia after intracisternal administration of bombesin. Administration of bombesin into the lateral ventricle of awake, unrestrained animals results in elevation of plasma glucose, preceded by a significant increase in plasma epinephrine and no increase in plasma norepinephrine or dopamine. Systemic administration of somatostatin prevents bombesin-induced hyperglycemia and hyperglucagonemia. These data support the conclusion that bombesin acts within the brain to increase sympathetic outflow resulting in increased adrenalmedullary epinephrine secretion, followed by depression of plasma insulin and elevation of plasma glucagon and glucose.
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PMID:Central nervous system action of bombesin: mechanism to induce hyperglycemia. 46 25

1. The effect of [D-Phe6] bombesin (6-13) methylester (OMe), a newly developed potent antagonist of bombesin receptors, has been investigated against bombesin-induced contractions of the guinea-pig and rat isolated urinary bladder. 2. Bombesin (0.1 nM-10 microM) produced a concentration-dependent contraction of the guinea-pig isolated bladder which approached the same maximum response as KCl (80 mM). The response to bombesin was antagonized in a competitive manner (rightward shift of the concentration-response curve without depression of the maximal response) by [D-Phe6] bombesin (6-13) OMe (0.3-10 microM). Degree of antagonism was concentration-dependent between 0.3 and 3 microM (dose ratios = 2.4, 9 and 39 in the presence of 0.3, 1, 3 microM of the antagonist). However, a larger concentration (10 microM) of the antagonist was not more effective (dose ratio = 36) than 3 microM. 3. Neither the action of bombesin nor the activity of the antagonist was influenced by peptidase inhibitors (bestatin, captopril and thiorphan 3 microM each) or by atropine, indomethacin, chlorpheniramine and desensitization of P2x purinoceptors by alpha, beta methylene ATP. 4. The bombesin antagonist was ineffective against contraction of the guinea-pig urinary bladder produced by the NK-1 tachykinin receptor-selective agonist, [Sar9] substance P sulphone. The action of the NK-1 receptor agonist was antagonized by L 668, 169 (3 microM), a cyclic peptide tachykinin antagonist. L 668, 169 had no effect toward bombesin-induced contraction. 5. The bombesin antagonist (1-10 microM) had no effect against the non-adrenergic non-cholinergic response of the guinea-pig isolated urinary bladder to electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of [D-Phe6] bombesin (6-13) methylester, a bombesin receptor antagonist, towards bombesin-induced contractions in the guinea-pig and rat isolated urinary bladder. 132 41

Hexadecylphosphocholine (HePC) inhibits protein kinase C (PKC) from NIH3T3 cells in cell-free extracts with a 50% inhibitory concentration of about 7 microM. Inhibition is competitive with regard to phosphatidylserine with a Ki of 0.59 microM. In order to determine whether HePC affects PKC in intact cells, the bombesin or tetradecanoylphorbolacetate-induced, PKC-mediated activation of the Na+/H(+)-antiporter was determined. It is demonstrated that HePC causes a drastic inhibition of this enzyme indicating a similar sensitivity of PKC to HePC in intact cells compared to cell-free extracts. In addition to the effects on PKC, treatment of NIH3T3 cells with HePC depresses the bombesin-induced formation of inositol 1,4,5-trisphosphate and the concomitant mobilization of intracellular Ca2+. Dose-response curves for the inhibition of inositol 1,4,5-trisphosphate formation and Ca2+ mobilization reveal 50% inhibitory concentrations of 2 or 5 microM, respectively. Polyphosphorylated phosphoinositides accumulate in HePC-treated cells indicating that the depression of inositol 1,4,5-trisphosphate generation is not caused by an inhibition of phosphoinositide kinases. Addition of bombesin to HePC-treated cells in the presence of LiCl revealed no evidence for an accelerated rate of inositol 1,4,5-trisphosphate turnover by the phospholipid analogue. It is concluded that HePC inhibits phosphoinositidase C in intact cells. The data strongly suggest that the growth-inhibitory effect of HePC is at least in part explained by the interference with mitogenic signal transduction.
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PMID:Hexadecylphosphocholine inhibits inositol phosphate formation and protein kinase C activity. 184 18

Expression of a transforming Ha-ras gene in NIH 3T3 cells transfected with an inducible Ha-ras construct leads to a rapid desensitization of the intracellular Ca2(+)-mobilizing system to bombesin and serum growth factors. Half-maximal depression of the Ca2+ response is observed 2 h after induction of p21ras. A maximum is obtained after 6 h. Bombesin-induced elevation of inositol 1,4,5-trisphosphate formation is also depressed in cells expressing Ha-ras. This, however, is a relatively late phenomenon and not yet detectable when maximal depression of the Ca2+ signal is observed. We conclude that the rapid densensitization of the Ca2(+)-releasing system to bombesin by Ha-ras is not caused by down-modulation or uncoupling of phospholipase C-coupled bombesin receptors. The inositol 1,4,5-trisphosphate-mediated release of intracellular Ca2+ is reduced in permeabilized cells expressing the Ha-ras oncogene. A depletion of intracellular Ca2+ stores by Ha-ras is unlikely since (i) the Ha-ras-induced growth factor-independent stimulation of inositol phosphate formation occurs several hours after reduction of the Ca2+ response and (ii) the Ca2+ load of intracellular nonmitochondrial Ca2+ stores was found to be unaffected by Ha-ras. We conclude that the desensitization of the Ca2(+)-mobilizing system is caused either by partial inhibition of inositol 1,4,5-trisphosphate-regulated Ca2+ channels or by interference of Ha-ras with Ca2+ translocation between intracellular Ca2+ compartments.
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PMID:Mechanism of desensitization of the Ca2(+)-mobilizing system to bombesin by Ha-ras. Independence from down-modulation of agonist-stimulated inositol phosphate production. 184 54

The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release.
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PMID:Role of gastrin in bombesin-stimulated somatostatin release. 197 61

Expression of the transforming Ha-ras oncogene in MMTV-LTR transfected NIH 3T3 cells leads to a growth factor independent activation of the Na+/H(+)-antiporter. The activation of the antiporter is insensitive to the protein kinase inhibitor staurosporine and equally expressed in protein kinase C-depleted cells. It is concluded that the Ha-ras induced activation of the antiporter occurs by a protein kinase C-independent mechanism. An inhibition of the Na+/H(+)-antiporter by dimethylamiloride or a reduction of the extracellular [Na+] concentration results in a depression of the bombesin induced release of Ca2+ from intracellular stores. These results are explained by a steep pH-dependence of the Ca2(+)-mobilizing system which exhibits a maximum at pH 7.1 in the system studied here. Stimulation by growth factors of quiescent cells with a resting pH below 7 results in a shift of the cytosolic pH towards the optimum for the Ca2+ release. In agreement with the proposed interrelationship, pHi and [Ca2+]i rise and peak simultaneously after addition of bombesin to G0 arrested cells.
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PMID:Mechanism and biological significance of the Ha-ras-induced activation of the Na+/H(+)-antiporter. 216

The effect of gamma-aminobutyric acid (GABA) on basal and bombesin (BBS)-stimulated release of somatostatin (SLI) and gastrin from isolated perfused rat stomach was examined. In the control study, BBS at a dose of 10 nM significantly stimulated release of SLI and gastrin. Infusion of GABA (1-1000 nM) caused a depression of SLI release induced by BBS (10 nM) in a dose-dependent fashion. However, at doses used in this study GABA had no effect on either basal level of SLI and gastrin or BBS-elicited gastrin release. These results indicate that GABA can specifically modulate BBS-induced SLI release from rat stomach.
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PMID:Effect of gamma-aminobutyric acid on bombesin-evoked release of somatostatin and gastrin from isolated rat stomach. 256 10

The effects of bombesin and related peptides on functionally identified single dorsal horn neurones were studied using iontophoresis and extracellular recording in the anaesthetized and spinalized cat. Bombesin selectively depressed superficial dorsal horn neurones (in laminae I-III). The depression was of spontaneous activity as well as of synaptically elicited responses to natural stimulation of the cutaneous receptive field. Bombesin preferentially depressed neurones that responded to noxious stimulation of the cutaneous receptive field. Naloxone, bicuculline and caffeine failed to block the depression by bombesin, suggesting that the effect of the peptide may be direct and not through the indirect activation of an inhibitory system mediated by opioids, by gamma-aminobutyric acid (GABA) or by purines, respectively. Iontophoretic application of neuromedin B (n = 3) and neuromedin C (GRP-10) (n = 7) induced a similar depression to that observed with bombesin. These results provide physiological evidence that a bombesin-like peptide may play a role in the mediation or the modulation of sensory transmission in the superficial dorsal horn of the spinal cord.
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PMID:Bombesin, neuromedin B and neuromedin C selectively depress superficial dorsal horn neurones in the cat spinal cord. 279 Apr 61

Siberian hamsters (Phodopus sungorous sungorous) decrease their food intake when exposed to short ("winter-like") photoperiods. The cause of this naturally-occurring hypophagia is unknown, but it may be due to a heightened sensitivity to the factors that normally terminate food intake in long photoperiods, such as the putative satiety peptides. The purpose of the present investigation was to test whether there would be an enhanced sensitivity to the inhibitory effects of some of these peptides on food intake in short relative to long days. Ad lib-fed, adult female Siberian hamsters were housed in a long photoperiod (LD 14:10) and injected with bombesin, glucagon, cholecystokinin octapeptide (CCK-8) and calcitonin (CT). Food intake was monitored 1, 2, 4, 6, and 24 hr post-injection. Bombesin and glucagon had no effect on food intake in long day-housed hamsters. CCK-8 and CT inhibited food intake; however, CCK-8 did so without any apparent behavioral disruption, while CT produced a marked and prolonged depression of behavior. After 10 weeks of exposure to a short photoperiod (LD 8:16) the hamsters were tested again. The previously ineffective dose of bombesin greatly inhibited food intake following short photoperiod exposure. In addition, an increased inhibition of food intake by CCK-8 was also found. In contrast, glucagon did not decrease food intake and CT still produced its non-specific, behaviorally disruptive effects. To our knowledge, this is the first demonstration that the effectiveness of a putative satiety peptide can be dependent upon a change in the photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Photoperiod-peptide interactions in the energy intake of Siberian hamsters. 356 18

Bombesin, some of its fragments and analogues, being injected intracerebroventricularly, induce rapid decline in body temperature. The active fragment of bombesin--C-terminal nonapeptide--induced a 25% depression of oxygen consumption in cold-exposed rabbits, no changes in the shivering thermogenesis, and a 3.5--5.0-fold increase of ear blood vessels section area accompanied by a gain in linear velocity of blood flow. The peripheral blood flow seems to be the main effector of the bombesin-induced hypothermia.
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PMID:[Bombesin reduces body temperature chiefly by increasing peripheral blood flow]. 356 72


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