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101.
The mechanisms of carbachol-induced muscarinic acetylcholine receptor (mAChR) down-regulation, and recovery following carbachol withdrawal, were studied in the neuroblastoma x glioma hybrid NG108-15 cell line by specific ligand binding assays. N-[3H]Methylscopolamine ([3H]NMS) and [3H]quinuclidinyl benzilate ([3H]QNB) were used as the ligands for the cell surface and total cellular mAChRs, respectively. Exposure of cells to 1 mM carbachol for 16 h decreased the specific binding of [3H]NMS and [3H]QNB by approximately 80%. Bacitracin (1-4 mg/ml) and methylamine (1-15 mM), inhibitors of transglutaminase and of endocytosis, prevented agonist-induced loss of surface mAChRs. Pretreatment of cells with the antimicrotubular agents nocodazole (0.1-10 microM) and colchicine (1-10 microM) prevented carbachol-induced loss of [3H]QNB binding, but not that of [3H]NMS binding. These results indicate that agonist-induced mAChR down-regulation occurs by endocytosis, followed by microtubular transport of receptors to their intracellular degradation sites. When carbachol was withdrawn from the culture medium following treatment of cells for 16 h, receptors recovered and were incorporated to the surface membrane. This recovery process was antagonized by monovalent ionophores monensin (0.1 microM) and nigericin (40 nM), which interfere with Golgi complex function. Receptor recovery was also prevented by the antimicrotubular agent nocodazole. Thus, recovery of receptors appears to be mediated via Golgi complex and microtubular transport to the surface membrane. 相似文献
102.
Brian Pearce Sean Murphy James Jeremy Christine Morrow Paresh Dandona 《Journal of neurochemistry》1989,52(3):971-977
Astrocyte cultures prelabelled with either [3H]inositol or 45Ca2+ were exposed to ATP and its hydrolysis products. ATP and ADP, but not AMP and adenosine, produced increases in the accumulation of intracellular 3H-labelled inositol phosphates (IP), efflux of 45Ca2+, and release of thromboxane A2 (TXA2). Whereas ATP-stimulated 3H-IP accumulation was unaffected, its ability to promote TXA2 release was markedly reduced by mepacrine, an inhibitor of phospholipase A2 (PLA2). ATP-evoked 3H-IP production was also spared following treatment with the cyclooxygenase inhibitor, indomethacin. We conclude that ATP-induced phosphoinositide (PPI) breakdown and 45 Ca2+ mobilisation occurred in parallel with, if not preceded, the release of TXA2. Following depletion of intracellular Ca2+ with a brief preexposure to ATP in the absence of extracellular Ca2+, the release of TXA2 in response to a subsequent ATP challenge was greatly reduced when compared with control. These results suggest that mobilisation of cytosolic Ca2+ may be the stimulus for PLA2 activation and, thus, TXA2 release. Stimulation of alpha 1-adrenoceptors also caused PPI breakdown and 45 Ca2+ efflux but not TXA2 release. The effects of ATP and noradrenaline (NA) on 3H-IP accumulation were additive, but their combined ability to increase 45Ca2+ efflux was not. Interestingly, in the presence of NA, ATP-stimulated TXA2 release was reduced. Our data provide evidence that functional P2-purinergic receptors are present on astrocytes and that ATP is the first physiologically relevant stimulus found to initiate prostanoid release from these cells. 相似文献
103.
Incubation of human bloodstream neutrophils with 50 u/ml recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) primed the respiratory burst (as assessed by fMet-Leu-Phe stimulated luminol-dependent chemiluminescence) and resulted in a rapid (within 15 min) upregulation of expression of CD11b and CD18 (as measured by FACS analysis). This rapid priming and modulation of receptor expression was not inhibited by cycloheximide and hence appeared to be independent ofde novo protein biosynthesis. When neutrophils were incubated for up to 5 h in culture, the fluorescence distributions of CD11b and CD18 declined indicating the loss of expression of these receptors as the neutrophils aged, but in rGM-CSF treated suspensions receptor expression was maintained. When neutrophils were incubated in the presence of cycloheximide, they progressively lost their ability to generate reactive oxidants in response to fMet-Leu-Phe so that by 5 h incubation with this inhibitor they could only generate about 25% of the oxidative response stimulated in untreated cells, and the expression of CD16 and CD18 was grossly impaired. Similar effects were observed in rGM-CSF treated suspensions except that cycloheximide required longer incubation times (typically 4–5 h) before impairment of function or receptor expression occurred. These data show thatde novo protein biosynthesis is required for both the maintenance of neutrophil function and also for the continued expression of some plasma membrane receptors.Abbreviations fMet-Leu-Phe
N-formylmethionyl-Leucyl-Phenylalanine
- rGM-CSF
recombinant granulocyte-macrophage colony-stimulating factor
- FITC
fluorescein isothiocyanate conjugate
- Luminol
5-amino-2,3-dihydrophthalazine-1,4-dione 相似文献
104.
We have tested the ability of several B2 antagonists on the responses of the open-circuited isolated canine tracheal epithelium to the luminal addition of Bradykinin (BK), Lys-BK, and substance P (SP). All three peptides produced biphasic changes in transmural potential difference (PD), an initial decrease (dip) followed by an increase (rise). The B2 antagonists
-Argo [Hyp3,Thi5,8,
-Phe7]BK (B5630) reversibly inhibited both the dips and the rise with IC50 values of 2.01 · 10−8 and 1.54 · 10−7 M, respectively. The responses to SP were unaffected even with high concentrations of the antagonist. Other antagonists tested [
-Phe1,7,Thi5,8]BK (B4158), [
-Phe2,7]BK (B4404), and [
-Phe7,Hyp8]BK (B5092) were ineffective. 相似文献
105.
Timothy K. Hayes Larry L. Keeley 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1990,160(2):187-194
Summary Several members of the adipokinetic/hyperglycemic neurohormone family from several different invertebrate species have been prepared by solid-phase peptide synthesis and assayed by a modified in vivo hyperglycemic bioassay in Blaberus discoidalis cockroaches. The hypertrehalosemic hormone (HrTH) is the endogenous hypertrehalosemic factor for B. discoidalis and was the most potent peptide in the assay. The more divergent the sequence of a family member from Blaberus HrTH, the less potent was the bioanalog. Manduca adipokinetic hormone is the most divergent peptide of the family and was totally inactive in the bioassay. Locusta adipokinetic hormone I had reduced maximum activity in the assay, which suggests that Ser5 is an important residue for the transduction of the hyperglycemic response. The direct relation between bioanalog similarity to Blaberus HrTH sequence and potency suggests that the hormone and target cell receptor for HrTH have evolved to maintain an optimal fit.Abbreviations
AKH
adipokinetic hormone
-
HrGH
hyperglycemic hormone
-
HrTH
hypertrehalosemic hormone
-
RPCH
red pigmentconcentrating hormone
- CAH
cardioacceleratory hormone. Hormone abbreviations are according to the convention of Gäde and Raina (1989) except that the genus names are not abbreviated 相似文献
106.
Angie Rizzino Peter Kazakoff John Nebelsick 《In vitro cellular & developmental biology. Plant》1990,26(5):537-542
Summary Previous studies have shown that cell density can regulate the binding of several growth factors. To determine whether cell
density exerts a uniform effect on the expression of epidermal growth factor (EGF) receptors, seven cell lines were examined
in detail. For each cell line, EGF binding was found to decrease as cell density increases. Scatchard analysis of the binding
data reveals that decreases in EGF binding are due to reductions in the number of cell surface EGF receptors. The only apparent
exception is the effect of cell density on the binding of EGF to A-431 cells. For these cells, increases in cell density lead
to two effects: decreases in the number of high affinity EGF receptors and increases in the total number of EGF receptors.
In addition to the effects of cell density on EGF receptors, it was determined that increases in cell density can coordinately
down-regulate receptors for as many as four different growth factors. Overall, the findings described in this report for EGF
and those previously described for transforming growth factor type-β (TGF-β) and fibroblast growth factor (FGF) demonstrate
the existence of a common mechanism for down-regulating growth factor receptors.
This work was supported by grants from the Nebraska Department of Health (89-51), the National Cancer Institute (Laboratory
Research Center Support Grant, CA36727), and the American Cancer Society (Core Grant ACS SIG-16).
EDITOR'S STATEMENT The paper by Rizzino et al. demonstrates that receptor number decreases as a function of cell density.
This may represent a mechanism by which cell proliferation is reduced as cell density increases. 相似文献
107.
Summary Fibronectin and heparin-binding growth factors (HBGF) are essential for growth of cultured endothelial cells. The stimulation
of endothelial cell growth by HBGF type one (HBGF-1) in particular requires heparin or a similar glycosaminoglycan. The requirement
for fibronectin and heparin for HBGF-1-stimulated endothelial cell growth may be related. HBGF-1 absorbed to the natural subcellular
matrix of endothelial cells supports cell growth. [125I]HBGF-1 specifically associates with a sequentially reconstituted matrix of collagen-fibronectin-heparin, and HBGF-1 absorbed
to the reconstituted matrix supports growth of the endothelial cells. A reconstituted matrix of collagen-laminin-heparin neither
supported binding of [125I]HBGF-1 nor HBGF-1-stimulated endothelial cell growth. Association kinetics of [125I]HBGF-1 to heparinlike sites and membrane receptor sites on endothelial cell monolayers suggest that fibronectin-heparinlike
binding sites in the subcellular matrix may be an obligatory reservoir of active HBGF-1 that binds to specific cell membrane
receptors.
This work was carried out in the laboratory of Dr. W. L. McKeehan and supported in part by grants CA37589, DK35310 and DK38639
from the Public Health Service, Department of Health and Human Services, Washington, DC. 相似文献
108.
Mark Phillippe Trevania Saunders Shrikar Bangalore 《In vitro cellular & developmental biology. Plant》1990,26(4):369-378
Summary The following studies were undertaken to develop a cultured uterine myocyte model which would allow further clarification
of the adrenergic signal transduction mechanisms utilized by these myocytes. After mechanical removal of the endometrium,
rabbit uterine myoctes were isolated by an overnight enzymatic disaggregation using collagenase and DNase I. The isolated
myocytes were maintained in culture in 75-cm2 flasks containing Waymouth's MB 751/1 medium-10% fetal bovine serum along with 10−8
M estradiol, penicillin, streptomycin, and Fungizone. The phase contrast and electron micrographic appearance of these cells
was consistent with that previously reported for smooth muscle myocytes in culture. Immunocytochemical studies utilizing monoclonal
anti-alpha-smooth muscle actin antibodies confirmed the presence of smooth muscle actin in these cultured myocytes. Western
blot studies similarly confirmed the presence of alpha-smooth muscle actin in rabbit myometrial tissue and the cultured myocytes,
both the primary and F1 generation. After prelabeling the myocytes with [3H]inositol, adrenergic stimulation experiments demonstrated alpha-1 receptor mediated stimulation of inositol phosphates.
Beta receptor stimulation experiments confirmed cAMP production in these cultured myocytes, and the ability of clonidine,
an alpha-2 agonist, to inhibit forskolin stimulated cAMP production confirmed the presence of functional alpha-2 adrenergic
receptors in these myocytes. In conclusion, these cultured rabbit uterine myocytes have provided an in vitro model which can
be utilized to further clarify the adrenergic receptor signal transduction mechanisms in genital tract smooth muscle.
This research was supported by grant HD-22063 from the National Institutes of Health, Bethesda, MD. 相似文献
109.
Sensory receptors of the ovipositor ofTrichogramma maidis are described. Sense organs are found on the 2nd valvifers (1 type), on the tip of the 3rd valvulae (2 types) and on the 1st valvulae (4 types). The nature and possible functions of these sensilla are discussed.
相似文献
110.
Giovanni Fontana Roberto De Bernardi Federico Ferro Anita Gemignani Maurizio Raiteri 《Journal of neurochemistry》1996,66(1):161-168
Abstract: l -Glutamate, NMDA, dl -α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainate (KA) increased the release of somatostatin-like immunoreactivity (SRIF-LI) from primary cultures of rat hippocampal neurons. In Mg2+ -containing medium, the maximal effects (reached at ∼100 µ M ) amounted to 737% (KA), 722% (glutamate), 488% (NMDA), and 374% (AMPA); the apparent affinities were 22 µ M (AMPA), 39 µ M (glutamate), 41 µ M (KA), and 70 µ M (NMDA). The metabotropic receptor agonist trans -1-aminocyclopentane-1,3-dicarboxylate did not affect SRIF-LI release. The release evoked by glutamate (100 µ M ) was abolished by 10 µ M dizocilpine (MK-801) plus 30 µ M 1-aminophenyl-4-methyl-7,8-methylenedioxy-5 H -2,3-benzodiazepine (GYKI 52466). Moreover, the maximal effect of glutamate was mimicked by a mixture of NMDA + AMPA. The release elicited by NMDA was sensitive to MK-801 but insensitive to GYKI 52466. The AMPA- and KA-evoked releases were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX) or by GYKI 52466 but were insensitive to MK-801. The release of SRIF-LI elicited by all four agonists was Ca2+ dependent, whereas only the NMDA-evoked release was prevented by tetrodotoxin. Removal of Mg2+ caused increase of basal SRIF-LI release, an effect abolished by MK-801. Thus, glutamate can stimulate somatostatin release through ionotropic NMDA and AMPA/KA receptors. Receptors of the KA type (AMPA insensitive) or metabotropic receptors appear not to be involved. 相似文献