Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells

2009 ◽  
Vol 87 (8) ◽  
pp. 624-632 ◽  
Author(s):  
Chi-Kong Yeung ◽  
Jessica Ka-Yan Law ◽  
Sze-Wing Sam ◽  
Sven Ingebrandt ◽  
Hang-Yung Alaster Lau ◽  
...  

To determine whether changes in membrane potential affect the extent of mast cell degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions in the absence or presence of potassium channel openers (KCOs). Changes were compared between the field potential (FP) and the amount of histamine released. The results demonstrated that (i) the onset and duration of FP, which reflects the hyperpolarizing nature of the response, increased as the concentration of compound 48/80 increased; (ii) both FP and the amount of histamine released increased as the concentration of compound 48/80 increased; (iii) although both KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine derivative) potentiated compound 48/80-induced increases in FP and histamine release, without compound 48/80, they had no effect on either parameter; (iv) both glibenclamide and charybdotoxin significantly attenuated the compound 48/80-induced increase in FP; and (v) glibenclamide was able to attenuate the KCO-induced potentiation of FP. The results show that drugs presumably causing hyperpolarization can affect histamine release from rat peritoneal mast cells. The effect of KCOs on compound 48/80-induced response appears to be potentiation in nature rather than synergism. It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders.

1975 ◽  
Vol 142 (2) ◽  
pp. 391-402 ◽  
Author(s):  
D Lawson ◽  
C Fewtrell ◽  
B Gomperts ◽  
M Raff

We have used ferritin-conjugated divalent and monovalent anti-Ig antibodies to study simultaneously, histamine secretion and the ultrastructural distribution and redistribution of Ig receptors on rat peritoneal mast cells. We conclude that (a) divalent anti-Ig is required for both receptor redistribution and for calcium-dependent degranulation and histamine release, (b) divalent anti-Ig induces patching and pinocytosis but not capping of Ig molecules, (c) neither capping nor pinocytosis are required for triggering and if clustering is necessary, then less than 10 Ig molecules are required per cluster, and (d) degranulation (and histamine release) is not an all or none response of the mast cell.


1997 ◽  
Vol 45 (10) ◽  
pp. 1379-1391 ◽  
Author(s):  
Gary R. Login ◽  
Ann M. Dvorak ◽  
Midori Yamakawa ◽  
Eleni C. Digenis ◽  
Naoko Tanda ◽  
...  

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1–10 sec after exposure to the secretogogue compound 48/80 (10 μg/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant ( p<0.01) increases in the area and number of chymase-immunoreactive vesicles per μ2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.


1985 ◽  
Vol 226 (1) ◽  
pp. 335-338 ◽  
Author(s):  
L M Amende ◽  
M A Donlon

Purified perigranular and plasma membranes isolated from rat peritoneal mast cells were examined for Ca2+- and Mg2+-dependent ATPase activity. Isolated perigranular membranes contained only a low-affinity Ca2+- or Mg2+-dependent ATPase (Km greater than 0.5 mM). The plasma membranes contained both a low-affinity Ca2+- or Mg2+-dependent ATPase (Km = 0.4 mM, Vmax. = 20 nmol of Pi/min per mg), as well as a high-affinity Ca2+- and Mg2+-dependent ATPase (Km = 0.2 microM, Vmax. = 6 nmol of Pi/min per mg).


1966 ◽  
Vol 124 (3) ◽  
pp. 379-395 ◽  
Author(s):  
Elmer L. Becker ◽  
K. Frank Austen

The ability of a number of p-nitrophenylethyl, alkyl phenylalkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the homocytotropic antibody-mediated release of histamine from rat peritoneal mast cells has been tested. The effectiveness of these same phosphonates against the activated first component of rat complement (C'1a) has also been investigated. The rat mast cell esterase activated by the reaction of antigen and homocytotropic antibody resembles chymotrypsin in its reactivity with the phenylalkyl and chloroalkyl phosphonate, but is unlike this protease in its greater responsiveness to the 5-aminopentyl phosphonate relative to the pentyl phosphonate. The antigen-homocytotropic antibody-activated mast cell esterase and chymotrypsin, thus, appear to be similar, but different enzymes; i.e., they are parazymes (see reference 4, p. 501). There are distinct differences in the pattern of inhibition given by the phenylalkyl and aminoalkyl and alkyl phosphonates of the homocytotropic antibody-mediated histamine release from rat peritoneal mast cells and from guinea pig lung slices. On the basis of these differences it is concluded that the esterases activated by the combination of antigen and homocytotropic antibody on the mast cells of the two species are not the same. The arithmetic dose response curve found for the action of the phosphonates on the antigen-induced histamine release from rat peritoneal mast cells contrasted sharply with the logarithmic relationship found when these same inhibitors acted on the guinea pig lung system. This suggests that in addition to the antigen-antibody-activated esterases being unlike, the detailed mode of histamine release from the mast cells of the guinea pig lung differs from that of the mast cells of the rat peritoneum. Distinct and large differences were found in the pattern of inhibition of histamine release from rat peritoneal mast cells and of rat C'1a given by the phenylalkyl, and chloroalkyl and alkyl phosphonates implying that esterase activated by the combination of antigen with the sensitized rat peritoneal mast cells is not C'1a. Thus, the results with the peritoneal mast cells lead to the same conclusion as the previous work with guinea pig lung slices; i.e., the antigen-antibody-activated esterase involved in the homocytotropic antibody-mediated release of histamine is not part of the complement system.


Phytomedicine ◽  
2008 ◽  
Vol 15 (10) ◽  
pp. 808-814 ◽  
Author(s):  
Y. Shen ◽  
E.C.K. Pang ◽  
C.C.L. Xue ◽  
Z.Z. Zhao ◽  
J.G. Lin ◽  
...  

2008 ◽  
Vol 3 (4) ◽  
pp. 1934578X0800300
Author(s):  
Alicia B. Penissi ◽  
María I. Rudolph ◽  
Mariano E. Vera ◽  
María L. Mariani ◽  
Juan P. Ceñal ◽  
...  

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine, DhL), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin, Xt) and a semisynthetic butenolide (3-benzyloxymethyl-5 H-furan-2-one, But) on mast cell histamine release induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (DhL, Xt or But) and then challenged with the mast cell activator compound 48/80. Concentration-response studies of mast cell histamine release evoked by compound 48/80, evaluation of mast cell viability and morphology studies by light microscopy were carried out. Biochemical and morphological studies showed the effectiveness of the above lactones to inhibit secretory responses of rat peritoneal mast cells. The present study provides evidence in favor of the hypothesis that DhL, Xt and But inhibit compound 48/80-induced histamine release from rat peritoneal mast cells. Our findings may provide an insight into the design of novel pharmacological agents that may be used to regulate the mast cell response.


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