Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of immunoreactive (ir)-bombesin in bovine adrenal medulla, isolated adrenal chromaffin cells and subcellular fractions of the adrenal medulla was demonstrated using a specific antibody to the synthetic peptide. High levels of ir-bombesin were detected in acid (HCl) extracts of the adrenal tissue (27 pmol/g) and isolated cells (0.35 pmol per 10(6) cells). Subpopulations of adrenal chromaffin cells were also obtained by centrifugation of the original cell preparation through a stepwise bovine serum albumin gradient (cell layers I, II and III). The highest concentration of ir-bombesin (0.77 pmol/10(6) cells) was found in a cell population (cell layer I) enriched in noradrenaline (adrenaline/noradrenaline ratio of 0.6). At the subcellular level, ir-bombesin was mainly concentrated in the secretory granules (0.61 pmol/mg protein) along with catecholamines (1097 nmol/mg protein), but a relatively high concentration of ir-bombesin (0.26 pmol/mg protein) was also found in the microsomal fraction. Isolation and high performance liquid chromatography (HPLC) analysis of adrenomedullary ir-bombesin revealed the presence of four molecular forms, one of them corresponding to gastrin releasing peptide (GRP), another one (major peak) eluting closely to synthetic neuromedin B and another one coeluting with GRP-(18-27). HPLC analysis of the molecular forms of ir-bombesin in the microsomes and secretory granules indicated that GRP- and neuromedin B-like materials can be generated between the two fractions.
 ...
PMID:Bombesin-like immunoreactivity in bovine adrenal medulla. 395 50

From a side fraction obtained in our previous isolation of neuromedin B from porcine spinal cord, we have purified another decapeptide that exhibits a potent stimulant effect on the smooth muscle preparation of rat uterus. By microsequencing and synthesis, the amino acid sequence of the peptide has been identified as: Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2. This peptide is found to be identical with the carboxy-terminal subsequence [18-27] of gastrin releasing peptide, and to display a potent contractile activity on rat uterus in the characteristic manner of bombesin. These facts strongly suggest that the peptide may be a neuromediator in the neural communication systems of mammals. We propose the name "neuromedin C" for this peptide, since it is closely related to "neuromedin B", recently identified as a bombesin-like mammalian peptide.
 ...
PMID:Neuromedin C: a bombesin-like peptide identified in porcine spinal cord. 654 86

Using AR4-2J rat pancreatic carcinoma cells, the effects of a novel bombesin (BN) receptor antagonist [D-F5Phe6, D-Ala11]BN(6-13)OMe (BIM26226) on BN- or GRP-stimulated amylase release and binding of radio-labeled bombesin-like peptides to these cells were examined and compared to [D-Phe6,Leu13 psi(CH2NH)Leu14]BN(6-14) (Psi Bn(6-14)), one of the most potent BN receptor antagonists presently known. BN and GRP both stimulated amylase release with EC50 values in the nanomolar range. Both antagonists were devoid of agonist activity when tested alone. BIM26226 was most potent, antagonizing BN- or GRP-stimulated amylase release with IC50 values in the nanomolar range, whereas Psi Bn(6-14) was approximately ten times less potent. With 125I-[Tyr15]GRP bound to these cells, the binding affinities were BIM26226 > GRP > Psi Bn(6-14) >> neuromedin B. BIM 22626 was not able to inhibit binding of radio-labeled CCK-33, gastrin-17 or VIP. These results suggest that BIM26226 is one of the most potent and specific bombesin receptor antagonists in vitro and seems to be a useful tool to define the physiologic role of GRP in vivo.
 ...
PMID:Effects of BIM26226, a potent and specific bombesin receptor antagonist, on amylase release and binding of bombesin-like peptides to AR4-2J cells. 753 56

Endothelial cells were isolated from rat brain microvessels and grown in vitro. They expressed a high density of [125I-Tyr4]bombesin receptor (Bmax = 0.9 pmol/mg protein) with an apparent Kd value of 10 nM. The pharmacological profile of inhibition of the specific [125I-Tyr4]bombesin binding [bombesin = neuromedin B > gastrin releasing peptide (GRP)] was consistent with the presence of a neuromedin-B-preferring receptor. Addition of bombesin, neuromedin B and GRP increased the activity of phospholipase C as measured by the production of total inositol phosphates and from intracellular Ca2+ measurements. They increase 86Rb+ uptake by the Na+, K+, 2Cl- cotransporter and by a charybdotoxin-sensitive, Ca(2+)-activated K+ channel and 22Na+ uptake by the Na+/H+ exchanger. The pharmacological profiles of activation of phospholipase C, Na+, K+, 2Cl- cotransport and Na+/H+ exchange by bombesin-like peptide were consistent with an involvement of the neuromedin-B-preferring receptor characterized in binding experiments. It is suggested that one of the actions of neuromedin B in brain vessels could be to control K+ secretion by the blood/brain barrier.
 ...
PMID:Properties and functions of a neuromedin-B-preferring bombesin receptor in brain microvascular endothelial cells. 758 82

Ionophoresis of the smaller bombesin-like peptides (gastrin releasing peptide [GRP]-(18-27), neuromedin B, and bombesin) evoked responses from 30-60% of hamster suprachiasmatic nucleus cells recorded in a hypothalamic slice preparation, depending on the circadian phase. We also demonstrated for the first time that the putative bombesin-like peptide receptor antagonists [D-F5,D-Phe6,D-Ala11]bombesin-(6-13)methyl ester (BIM 26226) and [D-Phe6,Des-Met14]bombesin-(6-14)ethyl amide can be applied ionophoretically to block physiological responses to bombesin-like peptides. Together with earlier findings, these results show that bombesin-like peptides administered by several methods can potently alter the firing rates of hamster suprachiasmatic nucleus neurons in vitro. These results indicate that bombesin-like peptides affect suprachiasmatic nucleus cells and could play a role in modulating suprachiasmatic nucleus-mediated circadian rhythm entrainment.
 ...
PMID:Effects of ionophoretically applied bombesin-like peptides on hamster suprachiasmatic nucleus neurons in vitro. 770 41

The aim of this study was to characterize the receptor(s) for bombesin (BN) and its homologues (gastrin releasing peptide, GRP; neuromedin B, NMB; neuromedin C, NMC) in guinea pig gallbladder muscle strips. Dose-dependent contractions were induced by all peptides tested (potency: BN = GRP > NMC > NMB, but with similar efficacy: BN = GRP = NMC = NMB). The contractions were resistant to tetrodotoxin, atropine, phentolamine, and propranolol. BN tachyphylaxis (1 microM) abolished subsequent contractile responses to BN, GRP and NMC; and partially antagonized the response to NMB (66 +/- 7% inhibition). NMB tachyphylaxis (10 microM) markedly inhibited subsequent contractile responses to NMB (78 +/- 5%); and partially antagonized the contractile response to BN (36 +/- 4%), GRP (31 +/- 12%) and NMC (22 +/- 2%). At 1 microM, both [D-Phe6, Des-Met14]-BN(6-14) ethylamide and ICI 216, 140, two BN receptor antagonists, reduced the contractile actions of BN (82 +/- 4% and 59 +/-8% inhibition, respectively), GRP (75 +/- 11% and 45 +/- 5%), and NMC (73 +/- 9% and 51 +/- 6%) while having no marked effect on NMB contractions. Our pharmacological approaches (receptor tachyphylaxis and differential antagonism) provide support for two types of receptors for BN-like peptides on guinea pig gallbladder smooth muscle: a GRP-preferring receptor and a NMB-preferring receptor.
 ...
PMID:Pharmacological analysis of receptors for bombesin-related peptides on guinea pig gallbladder smooth muscle. 780 Aug 49

Characterization of bombesin binding sites in healthy human lung was performed through direct binding techniques. There was limited binding in the absence of trypsin and chymotrypsin inhibitors, suggesting important activities of both enzymes in human lung and/or increased sensitivity of the bombesin sites toward them. In human lung membranes, bombesin, gastrin releasing peptide (GRP) and GRP-preferring bombesin receptor antagonists displaced [125I-Tyr4]bombesin binding with high affinities (36-177 nM), whereas neuromedin B possessed a lower affinity of 2878 nM. [D-F5Phe6,D-Ala11]bombesin-(6-13)-methyl ester, the most active GRP-preferring bombesin antagonist as yet reported, had the highest affinity among all antagonists tested whereas neuromedin B had the lowest affinity. These data demonstrate that the bombesin binding sites in the human lung are of the GRP-preferring type.
 ...
PMID:Gastrin releasing peptide-preferring bombesin binding sites in human lung. 788 24

Bombesin is a potent releaser of many gut and pancreatic hormones including gastrin, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP), cholecystokinin (CCK), enteroglucagon, and insulin. Three mammalian bombesin-like peptides, gastrin-releasing peptide (GRP), neuromedin C (NMC or GRP-10), and neuromedin B (NMB), and two bombesin receptor subtypes, GRP preferring and NMB preferring, have been characterized. We used a highly potent, selective antagonist of the GRP-preferring receptor, [D-Phe6]bombesine(6-13)-methylester ([D-Phe6]Bn(6-13)OMe), to determine the receptor subtype mediating bombesin-induced secretion of gastrin, GIP, PP, peptide YY (PYY), and insulin, as well as the importance of endogenous bombesin-like peptides in controlling basal secretion of these hormones. Unanesthetized rats received femoral vein infusion of saline, bombesin (10 nmol/kg/h), [D-Phe6]Bn(6-13)OMe (1000 nmol/kg/h), or bombesin plus [D-Phe6]Bn(6-13)OMe. Blood was withdrawn from jugular vein catheters before and 30 min after the start of infusions. Plasma gastrin, GIP, PP, PYY, and insulin were measured by specific radioimmunoassays. [D-Phe6]Bn(6-13)OMe alone reduced basal insulin levels by 28% (p < 0.05) but did not alter basal levels of plasma PP, GIP, PYY, or gastrin (p > 0.05 for each). Bombesin infusion significantly increased plasma levels of each hormone (p < 0.0001 for each). [D-Phe6]Bn(6-13)OMe completely blocked bombesin-induced increases in PP, insulin, and gastrin, and almost completely blocked increases in GIP and PYY (p < 0.01 for each). Our results suggest that (a) exogenous bombesin significantly stimulates PP, insulin, GIP, PYY, and gastrin secretion, (b) bombesin-induced secretion of these hormones is primarily mediated by the GRP-preferring receptor, and (c) an endogenous bombesin-like peptide acting at this receptor subtype plays an important physiological role in control of basal secretion of insulin but not PP, GIP, PYY, or gastrin.
 ...
PMID:Bombesin receptor subtype mediation of gastroenteropancreatic hormone secretion in rats. 793 51

The actions of the peptides bombesin (BN), gastrin releasing peptide (GRP), neuromedin C (NMC), litorin and neuromedin B (NMB) were studied on neurons in slices of rat brain maintained in vitro to determine the BN receptor type present in different brain areas. Intracellular and extracellular recordings were made from hypothalamic neurons on the border of the periventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) and from mesencephalic 5-HT sensitive neurons in the dorsal raphe nucleus. In the region of the brain containing the SCN and PVN, BN and the BN-related peptides excited 31 out of 77 neurons on which they were tested. There was little difference in the potency of the BN-related peptides as excitants of neurons, the EC50 being about 10 nM. The response to the peptides usually lasted between 5 and 15 min with little sign of desensitization. Using NMC, GRP and NMB as agonists, the equilibrium constant for the GRP receptor antagonist [D-Phe6]-BN-(6-13)-ethylamide was approximately 10 nM. The response to the peptides fully recovered on washout of the antagonist. The CCKB/gastrin receptor antagonist CI-988 (1 microM) had no effect on either GRP- or NMC-mediated excitation. In the dorsal nucleus 40 of 75 neurons were sensitive to the BN-related peptides. BN, [Tyr4]-BN, NMB and litorin, were 10-20 times more potent than GRP and NMC. The responses to the BN-related peptides were not blocked by the selective GRP receptor antagonists [D-Phe6]-BN-(6-13)-methylester, [DF5Phe6][D-Ala11]-BN-(6-13)-methylester and [D-Phe6]-BN-(6-13)- ethylamide.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Different types of bombesin receptors on neurons in the dorsal raphe nucleus and the rostral hypothalamus in rat brain slices in vitro. 798 44

Specific receptors for bombesin/gastrin releasing peptide (GRP) on the androgen-independent human prostate cancer cell lines PC-3 and DU-145 were characterized. No specific binding of 125I-[Tyr4]-bombesin to the androgen-dependent human prostate cancer cell line LNCaP was detectable. The binding of 125I-[Tyr4]-bombesin to PC-3 and DU-145 cells was found to be time- and temperature-dependent, saturable, and reversible. Scatchard analysis revealed a single class of binding sites with high affinity (Kd 9.8 x 10(-11) M for PC-3, and 9.1 x 10(-11) M for DU-145 cells at 25 degrees C) and with a binding capacity of 44,000 binding sites/cell and 19,000 binding sites/cell, respectively. Bound 125I-[Tyr4]-bombesin was rapidly internalized by PC-3 cells. The nonhydrolyzable GTP analog GTP-gamma-S caused a dose-dependent inhibition of 125I-[Tyr4]-bombesin binding to PC-3 and DU-145 cells, indicating that a G-protein (guanine nucleotide-binding protein) couples the bombesin receptor to intracellular effector systems. Bombesin and GRP(14-27) inhibited the binding of 125I-[Tyr4]-bombesin to both cell lines in a dose-dependent manner with inhibition constants (Ki) of 0.5 nM and 0.4 nM, respectively. Both cell lines express the bombesin/GRP preferring bombesin receptor subtype, since, in displacement studies, neuromedin B was more than 200 times less potent than bombesin and GRP(14-27) in inhibiting the binding of 125I-[Tyr4]-bombesin. Two synthetic bombesin/GRP antagonists, RC-3095 and RC-3110, powerfully inhibited the specific binding of 125I-[Tyr4]-bombesin with Ki 0.92 nM and 0.26 nM on PC-3 cells, and 3.3 nM and 0.89 nM on DU-145 cells, respectively. These findings indicate that the PC-3 and DU-145 human prostate cancer cell lines possess specific high-affinity receptors for bombesin/GRP, and are suitable models for the evaluation of the antineoplastic activity of new bombesin/GRP antagonists in the treatment of androgen-independent prostate cancer.
 ...
PMID:Characterization of high-affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC-3 and DU-145: internalization of receptor bound 125I-(Tyr4) bombesin by tumor cells. 802 9


<< Previous 1 2 3 4 5 Next >>