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1

Interaction of class A G protein-coupled receptors with G proteins

100%
Slusarz R., Ciarkowski J.
Acta Biochimica Polonica
|
2004
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tom 51
|
nr 1
A model for interaction of class A G protein-coupled receptor with the G protein Ga subunit is proposed using the rhodopsin-transducin (RD/Gt) prototype. The model combines the resolved interactions/distances, essential in the active RD*/Gt system, with the structure of Gta C-terminal peptide bound to RD* while stabilizing it. As­suming the interactions involve conserved parts of the partners, the model specifies the conserved Helix 2 non-polar X- - -X, Helix 3 DRY and Helix 7/8 NP- -Y- - F RD* mo­tifs interacting with the Gta C-terminal peptide, in compliance with the structure of the latter. A concomitant role of Gta and Gtγ C-termini in stabilizing RD* could po­ssibly be resolved assuming a receptor dimer as requisite for G protein activation.
2
Content available remote

Central and local (enteric) action of orexins

86%
Korczynski W., Ceregrzyn M., Matyjek R., Kato I., Kuwahara A., Wolinski J., Zabielski R.
Journal of Physiology and Pharmacology. Supplement
|
2006
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tom 57
|
nr 6
17-42
Orexin-A (OXA, hyprocretin-1) and orexin-B (OXB, hypocretin-2) are peptides derived from the same 130 amino acid long precursor (prepro-orexin) that bind and activate two closely related orphan G protein-coupled receptors. Orexins and their receptors were first discovered in the rat brain, and soon after that in peripheral neural structures, including the vagal nerve and enteric nervous system, and in other structures involving the gastrointestinal tract diffuse neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins and their receptors were also demonstrated in the testes, adrenals, kidneys and placenta. This review is focused on central and enteric actions. Originally, orexins were considered to be neurotransmitters that centrally stimulate food intake in animals and humans, but it soon became evident that their action is broader due to activation of a large number of neuronal pathways involved in energy homeostasis, sleep-awake behavior, nociception, reward seeking, food and drug addiction, as well as reproduction, cardiovascular and adrenal function. In the gastrointestinal tract, orexins have been found so far to affect gastrointestinal motility and gastric, intestinal and pancreatic secretions. The effects were observed following central (intraventricular) or local (intraluminal, intraarterial), but not peripheral (intravenous), administrations of orexins. Since the expression of orexins in the gastrointestinal tract is enhanced during fasting, and fasting reveals many of the orexin gastrointestinal effects, it seems probable that on the local level, orexins keep the gastrointestinal tract functions ready during fasting and play a role in brain-gut axis control.
3
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The effect of concomitant stimulation with cholecystokinin and epidermal growth factor on extracellular signal-regulated kinase (ERK) activity in pancreatic acinar cells

86%
Daniluk J., Dabrowski A.
Journal of Physiology and Pharmacology
|
2007
|
tom 58
|
nr 3
The transmission of extracellular proliferation and differentiation signals into their intracellular targets is mediated by a signaling cascade culminating in mitogen-activated protein kinase (MAPK) also known as ERK. In pancreatic acinar cells both cholecystokinin (CCK) and epidermal growth factor (EGF) are known to stimulate ERK. Regulatory interactions among individual receptor-coupled signaling cascades are critically important for establishing cellular responses in the face of multiple stimuli. The aim of our study was to evaluate the effect of concomitant stimulation of G protein-coupled receptors (GPCR) and EGF receptors on ERK activity in isolated pancreatic acinar cells. ERK activity was determined by means of Western-blotting, with the use of the antibody which recognizes active, tyrosine-phosphorylated kinase (pY-ERK). pY-ERK level was strongly elevated by 10 nM CCK-8, 100 µM carbachol (CAR), or 100 nM EGF. The addition of EGF to 60 min-lasting incubations of acini with CCK-8 or CAR caused abrupt decrease of pY-ERK level to 56 and 59% of control, respectively. Similar phenomenon was observed when short stimulation with CCK-8 or CAR was superimposed on the effect of EGF. After the addition of EGF to acini incubated previously with phorbol ester TPA, strong decrease in pY-ERK level was also observed. In conclusion, in pancreatic acinar cells, concomitant stimulation with CCK or CAR and EGF has strong inhibitory effect on ERK cascade. This inhibitory cross-talk may be mediated, at least partially, by protein kinase C (PKC). These mutual inhibitory interactions demonstrate novel mechanism for integration of multiple signals generated by activation of G-protein-coupled and growth factor receptors in pancreatic acinar cells.
4
Content available remote

A new membrane G protein-coupled receptor (GPR30) is involved in the cardiac effects of 17beta-estradiol in the male rat

72%
Filice E., Recchia A. G., Pellegrino D., Angelone T., Maggiolini M., Cerra M. C.
Journal of Physiology and Pharmacology
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2009
|
tom 60
|
nr 4
3-10
In the present study, we evaluated the transduction pathways involved in the cardiac effects elicited by 17ß-estradiol (E2) on the isolated, Langendorff perfused male Wistar rat heart. E2 and selective agonists for ER and ERß induced a dose-dependent reduction of contractility which was blocked by the ER inhibitor ICI 182,780. Moreover, the potential involvement of the novel membrane estrogen receptor GPR30 in mediating estrogen activity was determined using the selective GPR30 ligand G-1. Notably, specific inhibitors of ERK, PI3K, PKA, and eNOS transduction pathways abolished the cardiac responses to E2. Taken together, our data suggest that ER and ERß along with several signaling cascades are involved in the action of E2 on the male rat heart. Our results also point to a potential role of GPR30, however further evaluation is required in order to fully understand the contribution of the different estrogen receptors in mediating estrogen activity on cardiac performance.
5

The regulating function of heterotrimeric G proteins in the immune system

72%
Wang Y., Li Y., Shi G.
Archivum Immunologiae et Therapiae Experimentalis
|
2013
|
tom 61
|
nr 4
6

Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promissing targets in therapies of cancer and other diseases

72%
Gendaszewska-Darmach E.
Acta Biochimica Polonica
|
2008
|
tom 55
|
nr 2
227-240
Lysophospholipids have long been recognized as membrane phospholipid metabolites, but only recently lysophosphatidic acids (LPA) have been demonstrated to act on specific G protein-coupled receptors. The widespread expression of LPA receptors and coupling to several classes of G proteins allow LPA-dependent regulation of numerous processes, such as vascular development, neurogenesis, wound healing, immunity, and cancerogenesis. Lysophosphatidic acids have been found to induce many of the hallmarks of cancer including cellular processes such as proliferation, survival, migration, invasion, and neovascularization. Furthermore, autotaxin (ATX), the main enzyme converting lysophosphatidylcholine into LPA was identified as a tumor cell autocrine motility factor. On the other hand, cyclic phosphatidic acids (naturally occurring analogs of LPA generated by ATX) have anti-proliferative activity and inhibit tumor cell invasion and metastasis. Research achievements of the past decade suggest implementation of preclinical and clinical evaluation of LPA and its analogs, LPA receptors, as well as autotaxin as potential therapeutic targets.
7
Content available remote

Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions

72%
Tazoe H., Otomo Y., Kaji I., Tanaka R., Karaki S.-I., Kuwahara A.
Journal of Physiology and Pharmacology. Supplement
|
2008
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tom 59
|
nr 2
Short chain fatty acids (SCFAs) are the major anions in the large intestine. They are produced by a bacterial fermentation of dietary fiber. SCFAs are known to have a variety of physiological and pathphysiological effects on intestine. However, the mechanisms by which intraluminal SCFAs are sensed are not known. In 2003, two orphan G protein coupled receptors (GPRs), GPR41 and GPR43, have been cloned and demonstrated to be receptors for SCFAs. Thus, we had attempted to make antibodies raised against GPR43 and GPR41 to elucidate the roles of SCFAs on colonic functions. We have also evaluated the effects of SCFAs on colonic motility to define the physiological roles on luminal SCFAs. In rat and human colon, GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extract. By immunohistochemistry, GPR43 immunoreactivity was localized with enteroendocrine cells expressing peptide YY, whereas 5-HT immunoreactive enteroendocrine cells were not immunoreactive for GPR43. GPR41 immunoreactivity was also found in human colon. In functional studies, propionate and butyrate concentration-dependently (10 µM - 10 mM) induced phasic and tonic contractions in rat colonic circular muscle. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonists SB204070. However, acetate did not induce phasic or tonic contractions. Propionate-induced responses were not observed in mucosal free preparations. The present results suggest that the SCFA-induced physiological effects on colonic functions might be attributable to the activation of SCFA receptors on epithelial cells in the colon.
8
Content available remote

Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas

58%
Antushevich H., Pawlina B., Kapica M., Krawczynska A., Herman A. P., Kuwahara A., Kato I., Zabielski R.
Journal of Physiology and Pharmacology
|
2013
|
tom 64
|
nr 4
9

Structure-activity relationships for insect kinins on expressed receptors from a tick [Acari: Ixodidae] and a mosquito [Diptera: Culicidae]

58%
Taneja-Bageshwar S., Strey A., Zubrzak P., Pietrantonio P. V., Nachman R. J.
Pestycydy
|
2005
|
nr 3
55-59
10

Signal transmission via G protein-coupled receptors in the light of rhodopsin structure determination

58%
Ciarkowski J., Drabik P., Gieldon A., Kazmierkiewicz R., Slusarz R.
Acta Biochimica Polonica
|
2001
|
tom 48
|
nr 4
G protein-coupled receptors (GPCRs) transducing diverse external signals to cells via activation of heterotrimeric GTP-binding (G) proteins, estimated to mediate ac­tions of 60% of drugs, had been resistant to structure determination until summer 2000. The first atomic-resolution experimental structure of a GPCR, that of dark (in­active) rhodopsin, thus provides a trustworthy 3D prototype for antagonist-bound forms of this huge family of proteins. In this work, our former theoretical GPCR mod­els are evaluated against the new experimental template. Subsequently, a working hy­pothesis regarding the signal transduction mechanism by GPCRs is presented.
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