Role of Different Bombesin Receptor Subtypes Mediating Contractile Activity in Cat Upper Gastrointestinal Tract

Milusheva, E.; Kortezova, N; Mizhorkova, Z.; Papasova, M; Coy, David H.; Bálint, András; Vizi, E. Sylvester; Varga, Gábor

doi:10.1016/s0196-9781(97)00467-1

Cited by 32 publications

(76 citation statements)

References 28 publications

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“…Because these neurons release VIP, PACAP, and NO as motor transmitters to cause relaxation of circular muscle, it is unlikely that GRP acts as motor transmitter in these neurons, although it is possible that GRP could act a neuromodulator regulating the release of these other motor transmitters by a presynaptic action. Numerous studies demonstrate that GRP causes direct contraction of smooth muscle cells and muscle strips derived from the circular muscle layer (5,7,20,22,29,39). In the three-compartment preparation of rat colon used in the present study, addition of exogenous GRP to either the orad or caudad peripheral compartment caused contraction, sometimes followed by increased spontaneous activity (unpublished observations).…”

Section: Discussionsupporting

confidence: 54%

“…A developmental role of GRP and the BB 2 in villous growth and in colon cancer has also been recently demonstrated (6). The exception to the predominance of the BB 2 receptor in the gut is the esophageal smooth muscle of the rat and cat in which the contractile effect of GRP and NMB is mediated by the NMBpreferring BB 1 receptor subtype (21,29,31,42).…”

Section: Discussionmentioning

confidence: 91%

“…They have been shown to modulate the activity of the immune system, most notably macrophages (8), and have trophic effects on normal and neoplastic cells, including the autocrine stimulation of proliferation by smallcell lung cancer tumor cells (30). In the gastrointestinal tract, they have been shown to participate in the regulation of pancreatic enzyme and gastric acid secretion, stimulation of smooth muscle contraction, and stimulation of the release of a number of gut hormones, including gastrin (5,19,20,29,31,36,37).The response to GRP, NMB, and related peptides is mediated by four subtypes of BB receptors designated BB 1 through BB 4 , although BB 4 is only present in amphibians. All four receptors have been cloned, and BB 1-3 have been shown to share ϳ50% homology in amino acid sequence (2,5,12,21,31,43).…”

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confidence: 99%

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confidence: 99%

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Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex

Grider

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Grider, John R. Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex. Am J Physiol Gastrointest Liver Physiol 287: G1109 -G1115, 2004. First published August 5, 2004; doi:10.1152/ajpgi.00080.2004.-The physiological role of gastrin-releasing peptide (GRP) and of its cognate receptors in regulating the intestinal peristaltic reflex was examined in a threecompartment flat-sheet preparation of rat colon. Mucosal stimulation applied to the central compartment at high, but not low levels of intensity, induced GRP release in the caudad compartment where descending relaxation was measured, but not into the ascending compartment where ascending contraction was measured or into the central compartment where the stimuli were applied. The selective GRP (BB 2) receptor antagonist, [D-Phe 6 ,des-Met 14 ]bombesin6-14, inhibited descending relaxation and VIP release in the caudad compartment induced by high but not by low levels of stimulation applied to the mucosa in the central compartment. The selective neuromedin B (BB 1) receptor antagonist, BIM-23127, had no effect on descending relaxation or VIP release. Neither the BB 1 nor the BB2 antagonist had any effect on ascending contraction or substance P release in the orad compartment. Consistent with the effects of the antagonists on the peristaltic reflex, the BB2 antagonist but not the BB1 antagonist decreased the velocity of propulsion of artificial fecal pellets through isolated segments of guinea pig distal colon. The results indicate that GRP is selectively released from myenteric neurons in descending pathways during the peristaltic reflex and that it acts via BB2 receptors to augment the descending phase of the peristaltic reflex and propulsion. enteric nervous system; vasoactive intestinal peptide; neuromedin B; colon GASTRIN-RELEASING PEPTIDE (GRP) and neuromedin B (NMB) are mammalian neuropeptides that belong to a family of peptides that are structurally related to the amphibian peptides bombesin (BB), ranatensin, and phyllolitorin. These are grouped as one large family on the basis of similarity in the amino acid sequence of the COOH-terminal end of the molecule (reviewed in Refs. 5, 21, and 31). GRP is a 27-amino acid peptide and is most closely related to BB, sharing all but 1 of the last 10 amino acids at the COOH-terminal end. The COOH-terminal end of GRP ) exists as a separate entity, and it is termed neuromedin C (NMC). NMB is a 32-amino acid peptide and is more closely related to the amphibian peptide ranatensin, sharing all but one of the last seven amino acids of the COOH-terminal end. No mammalian homolog of phyllolitorin has yet been identified. NMB and GRP differ in only 3 of the last 10 COOH-terminal amino acids. GRP and NMB have been shown to have a wide variety of actions. In the central nervous system, they have been implicated in thermoregulation, satiety, and the regulation of circadian rhythm (1,26,31, 32). They have been shown to modulate the activity of the immune system, most notably ma...

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 91%

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confidence: 99%

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confidence: 99%

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Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex

Grider

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In this study, we have shown that treatment of CHO cells with the extracellular agonist bombesin, a bioactive peptide that has been implicated in regulated secretion (50) and cell motility (1,33), resulted in increased cellular levels of ARF6-GTP which were accompanied by the redistribution of ARF6 to the plasma membrane and peripheral actin rearrangements. This process was inhibited by ARF6(T27N), the dominant negative mutant of ARF6.…”

Section: Discussionmentioning

confidence: 88%

ADP-Ribosylation Factor 6 Regulates Actin Cytoskeleton Remodeling in Coordination with Rac1 and RhoA

Boshans¹,

Szanto²,

Aelst

et al. 2000

Molecular and Cellular Biology

166

158

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In this study, we have documented an essential role for ADP-ribosylation factor 6 (ARF6) in cell surface remodeling in response to physiological stimulus and in the down regulation of stress fiber formation. We demonstrate that the G-protein-coupled receptor agonist bombesin triggers the redistribution of ARF6-and Rac1-containing endosomal vesicles to the cell surface. This membrane redistribution was accompanied by cortical actin rearrangements and was inhibited by dominant negative ARF6, implying that bombesin is a physiological trigger of ARF6 activation. Furthermore, these studies provide a new model for bombesininduced Rac1 activation that involves ARF6-regulated endosomal recycling. The bombesin-elicited translocation of vesicular ARF6 was mimicked by activated G␣q and was partially inhibited by expression of RGS2, which down regulates Gq function. This suggests that Gq functions as an upstream regulator of ARF6 activation. The ARF6-induced peripheral cytoskeletal rearrangements were accompanied by a depletion of stress fibers. Moreover, cells expressing activated ARF6 resisted the formation of stress fibers induced by lysophosphatidic acid. We show that the ARF6-dependent inhibition of stress fiber formation was due to an inhibition of RhoA activation and was overcome by expression of a constitutively active RhoA mutant. The latter observations demonstrate that activation of ARF6 down regulates Rho signaling. Our findings underscore the potential roles of ARF6, Rac1, and RhoA in the coordinated regulation of cytoskeletal remodeling.The ADP-ribosylation factor (ARF) proteins comprise a group of five Ras-related GTPases that are thought to function as regulators of membrane traffic. In vitro, the ARF proteins function as cofactors in the cholera toxin-catalyzed ADP-ribosylation of Gs (21, 36), hence its name, and have also been shown to stimulate the activity of phospholipase D (4,6,16,25,31). ARF1 has been extensively investigated; it is localized to the Golgi apparatus and plays a critical role in the recruitment of coat proteins during the formation of transport vesicles, a process critical for maintaining the integrity of the secretory pathway (37). Recently, much attention has been focused on ARF6, the least-conserved ARF protein that shares 66% amino acid homology with ARF1. ARF6 is localized to the plasma membrane and endosomes depending on its nucleotide status and has been shown to regulate endocytic traffic at the cell periphery (8,42,45).Immunoelectron microscopy observations in CHO cells have revealed that expression of the GTP-bound constitutively activated mutant of ARF6, ARF6(Q67L), induced an elaboration of the plasma membrane and a depletion of recycling endosomal vesicles. In contrast, the expression of the dominant negative mutant of ARF6, ARF6(T27N), resulted in sequestration of ARF6 in the perinuclear recycling endosome, the distribution of which partially overlapped with that of transferrin receptors and cellubrevin (10). These findings, together with the observation that ARF6(T27N) ex...

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Effect of amino acid modifications on the molecular structure of adsorbed and nonadsorbed bombesin 6–14 fragments on an electrochemically roughened silver surface

Podstawka

2008

J Raman Spectroscopy

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This work used infrared absorption and Raman spectroscopy to determine the structure of seven modified fragments (residues 6-14 of the polypeptide chain) of bombesin (BN 6 -14 ). The peptides studied are cyclo[D-Phe 6 , These peptides are potent bombesin agonists useful in the treatment of tumors.Surface-enhanced Raman scattering (SERS) spectroscopy was also used to examine the behavior of these molecules on an electrochemically roughened silver surface. The SERS spectra reveal that substituting native amino acids in these molecules with synthetic ones changes their adsorption state slightly on an electrochemically roughened surface of silver. The peptides [D-Tyr 6 , b-Ala 11 , Phe 13 , Nle 14 ]BN 6 -14 and [D-Tyr 6 , b-Phe 11 , Phe 13 , Nle 14 OH]BN 6 -14 tend to adsorb strongly on this surface via C O fragment (∼1400 cm −1 ). The observed medium enhancement of the Trp 8 residue and amide bond Raman signals indicate further interactions between these fragments and the surface. [D-Phe 6 , Leu-NHEt 13 , des-Met 14 ]BN 6 -14 and [D-Cys 6 , Asn 7 , D-Ala 11 , Cys 14 ]BN 6 -14 are shown to be coordinated to the silver through -CONH-, C O, and the indole ring. The strongest SERS bands (∼1506, ∼1275, ∼1149, and ∼1007 cm −1 ) of [D-Phe 6 , Leu 13 --p-chloro-Phe 14 ]BN 6 -14 and [D-Phe 6 , b-Ala 11 , Phe 13 , Nle 14 ]BN 6 -14 suggest that these two peptides bind to the silver via Trp 8 and -CONH-. In the case of cyclo[D-Phe 6 , His 7 , Leu 14 ]BN 6 -14 , the formation of a peptide/Ag complex is confirmed by the strong SERS bands involving Trp 8 and -CONHvibrations, which are accompanied by a SERS signal due to the C O vibrations.For these analogs, the relative potency for inhibition of binding of 125 I-[Tyr 4 ]BN to rat pancreas acini cells was correlated with the behavior of the amide bond on the silver surface, while the contribution of the structural components to the ability to interact with the rGRP-R was correlated with the SERS patterns.

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Role of Different Bombesin Receptor Subtypes Mediating Contractile Activity in Cat Upper Gastrointestinal Tract

Cited by 32 publications

References 28 publications

Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex

Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex

ADP-Ribosylation Factor 6 Regulates Actin Cytoskeleton Remodeling in Coordination with Rac1 and RhoA

Effect of amino acid modifications on the molecular structure of adsorbed and nonadsorbed bombesin 6–14 fragments on an electrochemically roughened silver surface

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