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931.
VA Boundy RR Luedtke AL Gallitano JE Smith TM Filtz RG Kallen PB Molinoff 《Canadian Metallurgical Quarterly》1993,264(2):1002-1011
Serotonin (5-HT) potently contracts the fundus of the rat stomach; however, the associated transduction pathway has not been described fully. Experiments were performed in an attempt to gain insight into the coupling mechanism associated with this fundal 5-HT receptor. 5-HT-stimulated [35S]GTP gamma S binding to a protein which was recognized by anti-G alpha Z antiserum in a Mg(++)-dependent fashion. 5-HT increased [35S]GTP gamma S binding in the fundus, but not in the corpus of the rat stomach. 5-HT also enhanced the binding of [alpha-32P]GTP to the fundal protein and increased the hydrolysis of GTP to GDP in fundal membranes. The fundal protein which binds GTP is 25 to 29 kDa in size whereas the brain G alpha Z protein which is recognized by the anti-G alpha Z antibody is a 41 kDa protein. Mixing experiments revealed that the fundal guanine nucleotide binding protein does not appear to be a proteolytic product of the 41 kDa G alpha Z protein. Activating protein kinase C with phorbol-12-myristate, 13-acetate induced a concentration-dependent, noncompetitive inhibition of [35S]GTP gamma S binding to the fundal protein, and of 5-HT-induced contraction of fundal strips. Phorbol-12-myristate, 13-acetate did not alter carbachol- or KCl-mediated fundus contraction. Furthermore, the activation of [35S]GTP gamma S binding by serotonergic agonists and its inhibition by pharmacological antagonists corresponded to the known actions of these agents on contraction of fundal muscle. The results provide evidence that the 5-HT receptor in the rat stomach fundus is coupled directly or indirectly to a G alpha z-like protein which may mediate 5-HT-induced contraction in this tissue. 相似文献
932.
LA Turner S Polic RG Hoffmann JP Kampine ZJ Bosnjak 《Canadian Metallurgical Quarterly》1993,76(4):718-725
The actions of halothane (HAL) and isoflurane (ISO) on conduction and regional refractoriness were studied in infarcted canine hearts to compare their effects on reentry in vitro. In two anesthetic groups of 8 hearts, high and low dose effects were assessed using action potentials recorded from Purkinje fibers located in the nonischemic and ischemic regions. An extrastimulus technique was used to determine the relationship between delay of conduction of premature impulses into the more refractory ischemic region and induction of reentrant responses. At high doses (HAL 0.60 mM and ISO 0.64 mM, approximately 2.3 minimum alveolar anesthetic concentration [MAC]) both anesthetics decreased (P < or = 0.05) the effective refractory period for direct intracellular stimulation of nonischemic fibers (local ERP, initial control: 294 +/- 8 ms); the decrease with HAL (-29 +/- 6 ms) was smaller (P < or = 0.05) than with ISO (-50 +/- 7 ms). HAL and ISO also decreased (P < or = 0.05) the coupling interval of the earliest premature impulse which conducted into the infarct (system effective refractory period [SERP], control: 301 +/- 7 ms) by -31 +/- 11 and -44 +/- 8 ms, respectively. In contrast, the functional refractory period (FRP) in the ischemic region (control:354 +/- 4 ms) was increased by HAL (26 +/- 8 ms; P < or = 0.05) but decreased by ISO (-14 +/- 4 ms, P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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This study examined whether the pig CL contains specific tumor necrosis factor alpha (TNF alpha) receptors and compared the binding affinities and capacities of small and large cell membranes. Aliquots of membranes, isolated from intact or dispersed luteal tissue, were homogenized, and membrane protein content was quantified. Luteal membranes were assayed for specific TNF alpha binding by displacement analysis, with use of [125I]TNF alpha and varying concentrations of unlabeled TNF alpha. Preliminary experiments demonstrated that TNF alpha binding was maximal after incubation at 22 degrees C for 180 min. In addition, [125I]TNF alpha binding was displaced by TNF alpha, but not by other cytokines. Small cell membranes contained a TNF alpha binding site with an affinity (Kd = 11.6-19 nM) different (p < 0.05) from that of the binding site on large cell membranes (Kd = 56.2-99.6 nM). TNF alpha binding capacities were similar in small and large cell membranes. These data demonstrate that pig CL contain specific, saturable TNF alpha binding sites. The higher-affinity binding sites were localized in the small cell population, which contains predominantly endothelial cells and small luteal cells, suggesting that TNF alpha acts primarily on one or both of these cell types within the CL. 相似文献
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