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141.
Valerie J. Horn Paul A. Sheehy Miriam B. Goodman Indu S. Ambudkar 《Molecular and cellular biochemistry》1991,101(1):43-49
Intracellular Ca2+ mobilization events were assessed in mouse L cells, which contain native prostaglandin E1 receptors and transfected human 2 adrenergic receptors. Both Fura2 (single cell measurements) and Quin 2, (cuvette assays) were used to determine [Ca2+]i levels. Our results demonstrate that in the transfected cells there is a dose-dependent increase in [Ca2+]i in response to isoproterenol (0.1 nM–100 nM), which is inhibited by the -adrenergic antagonist, propranolol, and is a result of intracellular Ca2+ release. [Ca2+]1 in these cells was also increased by prostaglandin E1, 8 bromo cyclic AMP, and aluminum fluoride. Both 8 bromo cAMP and isoproterenol induced a rapid increase in the levels of IP1, IP2, and IP3. The data presented demonstrate that the elevation of intracellular cyclic AMP induces an increase in IP3 production which leads to an elevation in [Ca2+];. We propose that this cyclic AMP dependent activation of the IP3 generating system occurs at a post-receptor site.Abbreviations cAMP
Adenosine Cyclic 3-5-Monophosphate
- [Ca2+]i
intracellular [Ca2+]i
- 8 Br cAMP
8 Bromo Adenosine Cyclic 3-5-Monophosphate
- DAG
Diacylglycerol
- EGTA]
[Ethylene Bis (oxyethylenenitrilo)] Tetracetic acid
- BSA
Bovine Serum Albumin
- HBSS-H
Hanks' Balanced Salt Solution buffered with HEPES to pH 7.4
- HEPES
4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid
- PIP2
Phosphatidylinositol 4,5-bisphosphate
- IP2
Inositol 4 Phosphate
- IP2
Inositol 4,5 Bisphosphate
- IP3
Inositol Trisphosphate
- PGE1
Prostaglandin E1
- PBS
Phosphate Buffered Saline Solution 相似文献
142.
Gerd Wallukat Gyorgy Nemecz Tibor Farkas Hartmut Kuehn Albert Wollenberger 《Molecular and cellular biochemistry》1991,102(1):35-47
Incubation of rocker-cultured neonatal rat heart cells with 3 mM L(+)-lactate led to a sharp increase in the sensitivity of cardiomyocytes to the beta-adrenergic agonist isoprenaline, as measured by their chronotropic response. This effect was accompanied by a reduction in the arachidonic acid content of the total phospholipids. The phospholipase A2-activator melittin as well as free arachidonic acid induced this supersensitivity to the same degree. On the other hand, the L(+)-lactate-evoked supersensitivity could be blocked by the phospholipase A2 inhibitors mepacrine and n-bromophenacyl-bromide, suggesting an involvement of phospholipase A2 in the process of beta-adrenergic sensitization. The sensitizing action of arachidonic acid was blocked by the lipoxygenase inhibitors esculetin and nordihydroguaiaretic acid, but not by the cyclooxygenase inhibitor indomethacin. Supersensitivity was likewise evoked by 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), but not by 5-S-HPETE or 5-S-HETE. These findings suggest that the phospholipase A2-15-lipoxygenase pathway plays a role in the induction of beta-adrenergic supersensitivity in the cultured cardiomyocytes and point to a new physiological role of the lipoxygenase product 15-S-HETE.Abbreviations NDGA
nordihydroguaiaretic acid
- HETE
hydroeicosatetraenoic acid
- HPETE
hydroperoxyeicosatetraenoic acid 相似文献
143.
Jun-mo Chung Andrew N. Spencer 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,169(5):599-606
Summary Dopamine, which is present in nerve-rich tissues of the hydromedusa Polyorchis penicillatus, produces membrane hyperpolarization in identified motor neurons from this jellyfish. In this study we demonstrate that the inhibitory action of dopamine is mediated by conventional drug-receptor interactions which are reversible, saturable and specific. When 10 M dopamine was applied by micro-spritzing onto voltage-clamped (holding potential, –20 mV), cultured swimming motor neurons, an outward current of about 1 nA was evoked. Using this technique, we established a potency order for several amines: dopaminenorepinephrine>tyramine >octopamine>-phenylethylamine. Dopamine is effective at concentrations betweeen 1 × 10-8 and 1 × 10-3
M. Several dopamine receptor blockers such as fluphenazine, haloperidol and spiperone reduced the dopamine-induced current in a concentration-dependent manner. Although propranolol, a -adrenergic blocker, reduced the dopamine response and SKF 83566, a D1 blocker, increased the response, it appears that the dopamine receptors in these jellyfish neurons share pharmacological properties with mammalian D2 dopamine receptors. 相似文献
144.
A. Wenning R. L. Calabrese 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,168(1):53-61
Summary The nephridial nerve cells of the leech, Hirudo medicinalis, 34 sensory cells, each associated with one nephridium, are sensitive to changes in extracellular Cl- concentration, an important factor in ion homeostasis. Using single-electrode current- and voltage clamp and ion substitution techniques, the specificity and mechanism of Cl- sensitivity of the nephridial nerve cell was studied in isolated preparations. Increase of the normally low external Cl- concentration leads to immediate and sustained hyperpolarization, decrease of the frequency of bursts and decrease of membrane conductance. The response is halogen specific: Cl- can be replaced by Br–, but not by organic mono- or divalent anions or inorganic divalent anions.At physiological Cl- concentrations (36mM extra-cellular Cl-), the nephridial nerve cell has a high resting conductance for Cl- and the membrane potential is governed by Cl-. In high extracellular Cl- concentrations (110–130 mM), membrane conductance is low, most likely due to the gating off of Cl- channels. Under these conditions, membrane potential is dominated by the K+ distribution and the nephridial nerve cell hyperpolarizes towards EK.Abbreviations
NNC
nephridial nerve cell
-
V
m
membrane potential
-
E
Cl(k)
equilibrium potential for Cl (K)
-
IV-curve
current-voltage relationship 相似文献
145.
Pharmacological and biochemical characteristics of the partially purified -aminobutyric acid (GABA)B receptor using baclofen affinity column chromatography have been examined. The Scatchard analysis of [3H]GABA binding to the purified GABAB receptor showed a linear relationship and the KD and Bmax values were 60 nM and 118 pmol/mg of protein, respectively. Although GTP and Mg2+ did not affect on the GABAB receptor binding, Ca2+ significantly increased [3H]GABA binding to the purified GABAB receptor in a dose-dependent manner and showed its maximum effect at 2 mM. The enhancement of the binding by Ca2+ was found to be due to the increase of Bmax by the Scatchard analysis. The treatments with pronase and trypsin significantly decreased the binding of [3H]GABA, but phospholipase A2 had no significant effect on the binding. In addition, treatment with glycosidases such as glycopeptidase A and -galactosidase significantly decreased the binding of [3H]GABA to the purified GABAB receptor. These results suggest that purification of the solubilized GABAB receptor by the affinity column chromatography may result in the functional uncoupling of GABAB receptor with GTP-binding protein. Furthermore, the present results suggest that cerebral GABAB receptor may be a glycoprotein and membrane phospholipids susceptible to phospholipase A2 treatment may not be involved in the exhibition of the binding activity.Special issue dedicated to Dr. Eugene Roberts. 相似文献
146.
David B. Sattelle Sarah C. R. Lummis James F. H. Wong James J. Rauh 《Neurochemical research》1991,16(3):363-374
A GABA-operated Cl– channel that is bicuculline-insensitive is abundant in the nervous tissue of cockroach, in housefly head preparations and thorax/abdomen preparations, and in similar preparations from several insect species. Bicuculline-insensitive GABA-operated Cl– channels, which are rare in vertebrates, possess sites of action of benzodiazepines, steroids and insecticides that are pharmacologically-distinct from corresponding sites on vertebrate GABAA receptors. The pharmacological profile of the benzodiazepine-binding site linked to an insect CNS GABA-operated Cl– channel resembles more closely that of vertebrate peripheral benzodiazepine-binding sites. Six pregnane steroids and certain polychlorocycloalkane insecticides, which are active att-butylbicy-clophosphorothionate (TBPS)-binding sites, also differ in their effectiveness on vertebrate and insect GABA receptors. Radioligand binding and physiological studies indicate that in insects there may be subtypes of the GABA receptor. Molecular biology offers experimental approaches to understanding the basis of this diversity.Special issue dedicated to Dr. Eugene Roberts 相似文献
147.
148.
培养的卒中型自发性高血压大鼠(SHR_(sp))及其对照 WKY 大鼠主动脉平滑肌细胞(VSMC)上存在心房钠尿肽(ANP)的特异性受体,它们与~(125)I-ANP 的最大结合量(B_(max))是:SHR_(sp)3.65±0.13和 WKY 1.89±0.09 pmol/mg pr(P<0.01);解离平衡常数(Kd)值分别是72.6±10.2和42.0±4.8×10~(-12)mol/L(P<0.01)。 两种细胞内介导舒血管作用的第二信使、环磷酸乌苷(cGMP)的基础浓度无显著差异,对相同剂量 ANP 刺激引起 cGMP 分别增加139(SHRsp)和271(WKY)倍。可见 SHRsp 的 VSMC ANP 受体数量虽比 WKY大鼠增多,但对相同剂量 ANP 引起的 cGMP 增加反应及 ANP 受体的亲和力均显著降低。高盐培养液孵育24h 后,细胞表面 ANP 受体的亲和力改变不明显,但受体数量下调,SHRsp 和 WKY 大鼠分别降至对照的34.8±8.2%和38.6±9.4%,细胞对 ANP 引起的 cGMP增加反应明显降低,且均以 SHR_(sp)较显著。提示后两种变化可能在高盐促进血压升高的机制中起作用。 相似文献
149.
Binding of the labeled anticonvulsant drug [3H]dibenzocycloalkenimine (3H]MK-801) to the N-methyl-D-aspartate (NMDA) receptor and its dissociation from the receptor at 25°C are slow processes, both of which follow first order kinetics (t1/270 and 180 min, respectively). Both reactions are markedly accelerated by glutamate and glycine (t1/22-8 and 4 min, respectively), which allow bimolecular association kinetics of the labeled drug with the receptors whereas equilibrium binding of [3H]MK-801 (Kd 2–4 nM) is hardly affected by glutamate and glycine. The data suggest that MK-801 acts as a steric blocker of the NMDA receptor channel. The competitive antagonist D-(−)-2-amino-5-phosphovaleric acid (AP-5) freezes the receptor in a state which precludes either binding of [3H]MK-801 to the receptor channel or its dissociation from it. These findings have therapeutic implications. 相似文献
150.
A cDNA probe for the low density lipoprotein (LDL) receptor gene was used to screen DNA samples from 52 unrelated Finnish patients with the heterozygous form of familial hypercholesterolemia (FH) and 51 healthy controls. Southern blot analysis using the restriction enzyme PvuII revealed an abnormal 11 kb (kilo base-pair) restriction fragment in 16 (31%) of the patients but none of the controls. A more detailed restriction enzyme analysis of the DNA from patients revealed a mutation which apparently is due to an 8 kb deletion extending from intron 15 to exon 18 of the LDL receptor gene. Co-segregation of FH with the mutated gene was demonstrated in three families. These data are consistent with a ‘founder gene effect’ and support the assumption that recombinant DNA methods may have great impact on the diagnostics of FH in genetically homogeneous populations. 相似文献