Binding of 3H-5-hydroxytryptamine to synaptic plasma membranes of rat brain.
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Biomedical subjects
Publications and source records attributed to J Gripenberg.
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The effects of halothane, thiopental, and lidocaine were studied with spin-labeling methods in synaptic plasma membranes (order parameter) and artificial phospholipid membranes (lateral diffusion). Halothane had a biphasic action, low concentrations (0.64 mM) ordering and high concentrations (2.9 mM) fluidizing both types of membranes. A biphasic effect in phospholipid membranes was also seen with thiopental, 0.1 mM ordering and 10 mM fluidizing, whereas in synaptic plasma membranes both low and high concentrations caused an increased order in the lipid bilayer region. At high thiopental concentrations, a considerable number of molecules may have reacted with membrane proteins or accumulated in the highly fluidic hydrophobic interior region of the membrane without affecting the rotational movement of the labeled fatty acid. Lidocaine alone, or together with calcium chloride, at various concentrations to 10 mM had no significant effect, and a fluidizing effect of 1 mM calcium chloride was possibly a result of interaction of calcium chloride with the label. The results indicate that the three lipid-soluble anesthetics interact differently with the lipid part of membranes. Lidocaine did not seem to affect bilyer lipids, while thiopental and halothane in phospholipid vesicles and halothane alone in synaptic membranes caused a dose-dependent biphasic effect.
The effect on tissue catecholamines of blockade of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) was studied in the rat. 6-AN at 35-50 mg kg-1 persistently lowered the adrenaline content in the adrenal gland to less than 10% of control values and caused a 50% loss of noradrenaline, which recovered. When the amine turnover rate was increased by a preceding period of drum stress, 6-AN also consistently depressed noradrenaline in the gland. 6-AN was without significant effect on the noradrenaline concentration in heart tissue, hypothalamus and superior cervical ganglion and did not affect the uptake or release of catecholamines in vitro. The possibility is discussed that 6-AN interferes with the biosynthesis of catecholamines, when it blocks the pentose phosphate pathway, by decreasing the supply of reducing equivalents in the form of NADPH which are necessary for the tetrahydropteridine cofactors of tyrosine hydroxylase.
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1 The effect of prostaglandin E1 on neuromuscular transmission in the phrenic nerve-diaphragm muscle preparation of the rat was studied with intra- and extracellular recording techniques. 2 Prostaglandin E1, in concentrations from 10 nM, induced intermittent failures in the generation of the end-plate potential in response to repeated indirect stimulation. 3 Failures appeared abruptly, the end-plate potential behaving in an all-or-nothing fashion. The effect occurred only at 36-38 degrees C when the nerve was stimulated at 30-80 Hz and was reversible upon washing with drug-free solution. 4 Since miniature end-plate potentials were not affected, such failures must be attributed to a presynaptic action of prostaglandin E1. 5 Extracellular recording suggested that prostaglandin E1 prevented the action potential from reaching the nerve terminal.
The effect of reserpine, guanethidine and imipramine of the uptake of tritiated 5-hydroxytryptamine by rat peritoneal mast cells was studied in vitro. The Km value for uptake of 5-hydroxytryptamine was 3 x 10(-7) M in this study. Kinetic analysis of the data obtained suggests that the drugs inhibits the uptake in a competitive manner, in the order of decreasing potency: reserpine, imipramine, guanethidine. For reserpine the Dixon plot resulted in two curves, each composed of 2 linear components suggesting inhibition of uptake of 5-hydroxytryptamine at 2 different levels or by 2 different mechanisms with different K1 values. It is suggested that the higher K1 value, representing an immediate effect of reserpine, stands for inhibition of uptake at the cell membrane. The lower K1 value possibly represents inhibition at the level of the membrane surrounding the intracellular storage organelles.
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Eighty-eight patients with 105 foci of bacterial infection were investigated by 111In-granulocyte scintigraphy. The overall sensitivity of this method was 74 per cent. A negative correlation between duration of signs and symptoms and the intensity of the granulocyte accumulations was found, and patients having false negative scintigraphy also had a significantly longer history of infection, clearly demonstrating the importance of performing scintigraphy in the acute phase of an infection. Scintigraphy performed after negative or equivocal computed tomography (CT) or ultrasound (US) investigations in patients with strongly suggested occult infection revealed many foci of infection, particularly in areas not covered by CT or US, showing the superiority of 111In-granulocyte scintigraphy over the two other methods when localizing symptoms are absent.