摘要:

Summary—Specific binding of L‐[3H]glutamate was measured in Tris‐HCl buffer in rat hippocampal membranes. In these experimental conditions 1 mM CaCl2induced an increase in binding due to an increase in Bmax.L‐Arginine methylester did not modify the Cl−‐dependent binding of L‐[3H]glutamate, but it decreased Ca2+/Cl−‐stimulated binding in a dose‐dependent manner, decreasing Bmaxwithout changing KD. L‐Arginine methylester reduced calcium‐activated neutral protease activity in a dose‐dependent manner. Serine protease inhibitors (aprotinin and di‐isopropylfluorophosphate) did not affect L‐[3H]glutamate binding, whereas leupeptin reduced it in a dose‐dependent manner. L‐Arginine did not mimic the effect of L‐a

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00567.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Intracarotid (IC) injection of bestatin produced a dose‐dependent biphasic change in blood pressure (BP) of the rat, consisting of an initial short‐lasting fall followed by a long‐lasting increase. This effect was regularly depressed or abolished by IV injection of naloxone. IC injection of Leu‐enkephalin also produced a biphasic BP response, with the same characteristics as that produced by IC injection of bestatin. This effect was also easily blocked by IV injection of naloxone. IC injection of bestatin significantly potentiated the BP response to IC injection of Leu‐enkephalin. This potentiated response was blocked by naloxone. IC injection of both bestatin and phosphoramidon, whether separately or in combination, significantly depressed the hypertensive response to physostigmine. This depressive action of bestatin and phosphoramidon on physostigmine hypertension can be significantly antagonized or even reversed by IV injection of naloxone. IC injection of both bestatin and phosphoramidon did not affect the BP response to either acetylcholine or catecholamines. It is concluded that bestatin and phosphoramidon, injected into the carotid artery, inhibit the activity of aminopeptidase and «enkephalinase», thus producing an accumulation of enkephalins in the central nervous system. These enkephalins activate opioidergic receptors in the brain, but concomitantly produce a depression of the cholinergic‐adrenergic interaction in the central nervous system, which is known to be a prerequisite for the hypertensive response to physostig

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00568.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The localization and pharmacologic characterization of muscarinic receptors possibly regulating the release of dopamine (DA) in rat corpus striatum were investigated byin vitrobinding with [3H]pirenzepine ([3H]PZ) after hemitransection of the nigro‐striatal pathway. DA levels in the corpus striatum ipsilateral to the lesion were substantially reduced by 66% compared with the unlesioned side after 8 days. The uptake of [3H]DA was also diminished by 63%. A significant decrease in the specific binding of [3H]PZ of 42% was seen in the corpus striatum ipsilateral to the lesion. The data indicate a loss of binding sites, whereas the lesion caused no change in the affinity constant for the muscarinic antagonist. The results support those previously obtained in studies of the muscarinic modulation of [3H]DA release from striatal synaptosomes and favor the idea that at least part of the muscarinic receptors regulating striatal DA release are localized on the nigro‐striatal axon terminals and belong to the pirenzepine‐sensitive

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00569.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine ([3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard.Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmaxof the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknow

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00570.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The systemic and coronary hemodynamic actions of a newly synthesized inotropic agent structurally related to milrinone and amrinone, MCI‐154 (0.5‐4.0 μg/kg/min IV), were studied in 2 groups of conscious, chronically instrumented dogs with normal or depressed postischemic, reperfused myocardium after a 15‐min coronary artery occlusion. In an additional group of control experiments, the time course of recovery of postischemic, reperfused myocardium was studied to verify the constancy of regional segment shortening in the previously ischemic zone during the time corresponding to drug infusion. Similar inotropic actions of MCI‐154 were observed in both normal and postischemic, reperfused hearts, indicating significant contractile reserve to be present in ‘stunned’ myocardium. Global contractility as measured by peak positivedP/dt was significantly increased in both groups. In postischemic, reperfused myocardium 90 min after initiation of reflow, regional segment function remained depressed at 44% of control but improved to 93% of control after administration of MCI‐154. In addition, MCI‐154 produced significant dose‐related decreases in mean arterial pressure, left ventricular end‐diastolic pressure, end‐diastolic segment length, and diastolic coronary vascular resistance. The data demonstrate that in addition to producing beneficial hemodynamic changes, MCI‐154, a new non‐sympathomimetic inotropic agent, markedly enhances regional contractility of postisc

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00571.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The effect of 1, 25‐dihydroxycholecalciferol [1, 25(OH)2D3], the active form of vitamin D3, on cell growth, clonogenicity, and cyclic adenosine monophosphate (cAMP) production was examined in human breast cancer cell line T47D. 1,25(OH)2D3markedly inhibited proliferation of T47D cells in a time‐ and concentration‐dependent manner. 1,25(OH)2D35 times 10−7reduced to 70% [3H]thymidine incorporation into DNA. Specific high affinity nuclear receptors for 1,25(OH)2D3were present in this cell line. The cAMP produced by T47D cells was measured during 10 min stimulation by effectors (prostaglandin E1or forskolin). Without effector, T47D cells produced similar amounts of cAMP in control and 1,25(OH)2D3‐treated cells. After 3 days in the presence of 1,25(OH)2D3, cAMP production was significantly increased compared to control cells when stimulated by 10−4M prostaglandin E1or 5 times 10−7M forskolin (3.2‐ and 2.4‐fold increase, respectively). This cAMP increase was concentration dependent within the same range that inhibited cell growth and clonogenicity. These results suggest that 1,25(OH)2D3may indirectly affect cAMP production by modulating the target cell response to stimulatory agents

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00572.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00573.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY