Bicuculline and picrotoxin block gamma-aminobutyric acid-gated Cl- conductance by different mechanisms

Using isolated, internally perfused bullfrog dorsal root ganglion cells we have studied the dose-response curves for gamma-aminobutyric acid (GABA) in the presence of internally or externally applied GABA antagonists. With external application of antagonists the inhibition of the GABA current by bicuculline was competitive and that by picrotoxin was noncompetitive. Picrotoxin but not bicuculline blocked when internally perfused.     

Normetanephrine and metanephrine oxidized by both types of monoamine oxidase

Summary Both normetanephrine and metanephrine were found to be oxidized by both types of monoamine oxidase in mouse liver mitochondria. Both K_m and V_max values of type B MAO for both substrates were higher than those of type A MAO, which caused the shift of inhibition curves with clorgyline and deprenyl according to the increase in substrate concentration.     

Compartmentalization of sickle-cell calcium in endocytic inside-out vesicles

Much recent interest in the mechanism of dehydration of the dense subpopulation of sickle-cell anaemia (SS) red cells, including the 'irreversibly sickled cells' (ISCs), stems from the view that these relatively rigid cells have a major role in the two main clinical features of the disease, namely haemolytic anaemia and microvascular occlusion. The discovery that SS red cells have an elevated calcium content and accumulate Ca2+ during deoxygenation-induced sickling suggested a working hypothesis of wide appeal for the mechanism of cell dehydration: retained calcium would activate the red cell Ca2+-sensitive K+ channels, causing progressive net loss of KCl and water. However, retained calcium, which seemed as weakly bound to cytoplasmic buffers as in normal red cells, failed to show any measurable activation of K+ channels or Ca2+ pumps in metabolically normal SS cells, despite the apparent functional normality or near-normality of these transport systems. We now offer a possible explanation for this failure. We show that, contrary to the traditional views, SS cells, and to a lesser extent normal human red cells, possess intracellular vesicles with ATP-dependent Ca2+-accumulating capacity, and that nearly all the measurable calcium of fresh SS cells is contained within such vesicles, probably in the form of precipitates with inorganic or organic phosphates.     

Role of calcium in the histamine release induced by D-galactosamine from rat mast cells

Rat peritoneal mast cells were isolated and purified by differential centrifugation in Ficoll. Cells pooled from three to four rats were suspended at approximately 10(6) cells/ml in a buffered salt solution and incubated for 1 h at 37 degrees C in 300 microliter volumes in the absence or presence (9 X 10(-4) M) of calcium chloride. Addition of D-galactosamine hydrochloride (DGM; 2.8 X 10(-4)M) caused (in addition to basal release) a mean +/- SEM percent histamine release of 15.7 +/- 5.2 in the presence of Ca++ and 19 +/- 4.9 in the absence of Ca++ (p greater than 0.05). It is suggested that D-galactosamine does not require extracellular Ca++ for the release of histamine from the rat mast cell.     

Agent-oriented Aid-modeling for the Distributed Activity Network

1　 IntroductionModern system characters distributed problem solving from the view of new generation ofDSS.Thus,traditional DSS(P.Sage,1 992 ) will separate the system into4 main parts atdifferent allocation,so that it needs an environment of information technologies (R.Blanning,1 995) and the supportoforganizational connectivity(M.Jeusfeld,1 997) .Atthesame time,distributed decision processing requires coalescent problem modeling andcollaborated decision.The distributed problem solves in…     

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.     

Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action

The study demonstrated a decreased level of glucocorticoid receptors (GR) in peripheral blood lymphocytes from hypercholesterolemic subjects, and an elevated level in patients with acute myocardial infarction. In the lymphocytes with a high GR number, dexamethasone inhibited [3H]-thymidine and [3H]-acetate incorporation into DNA and cholesterol, respectively, in the same manner as in the control cells. On the other hand, a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds. These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level.     

Depressor effects of muscarinic and non-muscarinic mediation induced by lateral hypothalamic stimulation in the rat

Summary Transient sympathetically-mediated depressor effects were induced by stimulation of a small locus in the lateral hypothalamic peri-fornical region, medial to the fields of Forel. The ganglionic blocking agent, atropine methyl nitrate (ATMN), was used to show that muscarinic as well as non-muscarinic sympathetic ganglion receptor neurotransmission was involved. Evidence is presented that stimulation of this LH site co-activates a number of mechanisms and that depending on which of these are activated, the ganglionic blocking agent ATMN may either block, reverse or potentiate the depressor effect.     

Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle

Four days following an 8-h advance of the light-dark cycle, the circadian rhythms in the pineal N-acetyltransferase activity and melatonin content reappeared in 7-week-old rats, but were still abolished in 24-month-old animals.