scholarly journals STUDIES ON THE MECHANISM OF HYPERSENSITIVITY PHENOMENA

1959 ◽  
Vol 110 (2) ◽  
pp. 311-339 ◽  
Author(s):  
Abraham G. Osler ◽  
Harry G. Randall ◽  
Betsy M. Hill ◽  
Zoltan Ovary

The interaction of fresh rat and guinea pig serum with washed preformed immune aggregates has been studied with respect to the loss in hemolytic potency of the serum, diminution of the C'3; activity, and appearance of anaphylatoxin. It has been found that the formation of anaphylatoxin, as judged by its effect on capillary permeability and smooth muscle contraction, is coincident with or subsequent to the fixation of all the known C' components. Less anaphylatoxin is formed by aggregates formed with excess antigen than those in equivalence ratio combination. C' fixation, as well as anaphylatoxin production, may be inhibited by chelation of the divalent cations, presumably by interfering with the fixation of C'1, C'4, and C'2. Phlorizin suppresses the utilization of C'3 in immune hemolysis, C' fixation by antigen-antibody aggregates, and the production of anaphylatoxin. The biological activities associated with the fixation of C' are not manifest unless C'3 participates in this process at 37°C. It is concluded that the formation of anaphylatoxin may be regarded as a product of C' fixation.

1981 ◽  
Vol 241 (3) ◽  
pp. C130-C133 ◽  
Author(s):  
S. R. Findlay ◽  
L. M. Lichtenstein ◽  
D. J. Hanahan ◽  
R. N. Pinckard

Acetyl glyceryl ether phosphorylcholine (AGEPC) is a chemical that has the biological activity of what was formerly termed platelet-activating factor. We report here that synthetic AGEPC induces the contraction of guinea pig ileal smooth muscle. Antagonists of histamine, acetylcholine, and slow-reacting substances (SRS) do not block AGEPC-induced contraction. These responses were long lasting, resistant to washing, and displayed complete agonist specific desensitization. Histamine- and SRS-induced contractions were unaffected by AGEPC. These studies show that AGEPC has the potential to produce a component of anaphylactically induced smooth muscle contraction.


2007 ◽  
Vol 292 (3) ◽  
pp. G887-G898 ◽  
Author(s):  
Daniel P. Poole ◽  
John B. Furness

PKC is involved in mediating the tonic component of gastrointestinal smooth muscle contraction in response to stimulation by agonists for G protein-coupled receptors. Here, we present pharmacological and immunohistochemical evidence indicating that a member of the novel PKC isoforms, PKC-δ, is involved in maintaining muscarinic receptor-coupled tonic contractions of the guinea pig ileum. The tonic component of carbachol-evoked contractions was enhanced by an activator of conventional and novel PKCs, phorbol 12,13-dibutyrate (PDBu; 200 nM or 1 μM), and by an activator of novel PKCs, ingenol 3,20-dibenzoate (IDB; 100 or 500 nM). Enhancement was unaffected by concentrations of bisindolylmaleimide I (BIM-I; 22 nM) that block conventional PKCs or by a PKC-ε-specific inhibitor peptide but was attenuated by higher doses of BIM-I (2.2 μM). Relevant proteins were localized at a cellular and subcellular level using confocal analysis. Immunohistochemical staining of the ileum showed that PKC-δ was exclusively expressed in smooth muscles distributed throughout the layers of the gut wall. PKC-ε immunoreactivity was prominent in enteric neurons but was largely absent from smooth muscle of the muscularis externa. Treatment with PDBu, IDB, or carbachol resulted in a time- and concentration-dependent translocation of PKC-δ from the cytoplasm to filamentous structures within smooth muscle cells. These were parallel to, but distinct from, actin filaments. The translocation of PKC-δ in response to carbachol was significantly reduced by scopolamine or calphostin C. The present study indicates that the tonic carbachol-induced contraction of the guinea pig ileum is mediated through a novel PKC, probably PKC-δ.


1996 ◽  
Vol 270 (1) ◽  
pp. L133-L140 ◽  
Author(s):  
M. E. Strek ◽  
F. S. Williams ◽  
G. J. Gleich ◽  
A. R. Leff ◽  
S. R. White

Cationic proteins elicit contraction of airway smooth muscle, but the mechanisms by which this occurs are not completely understood. We studied potential mechanisms by which eosinophil major basic protein (MBP) and the synthetic cationic proteins poly-L-lysine (PL) and poly-L-arginine (PA) cause contraction of isolated guinea pig tracheal smooth muscle (TSM) in vivo. Topical application of 10(-8) mol/cm2 of each protein to an isolated tracheal segment elicited TSM contraction with potency PL > MBP > PA. Pretreatment with atropine blocked the subsequent response to MBP but did not block the response to either PL or PA. Pretreatment with indomethacin blocked the subsequent response to both MBP and PL but did not block the response to PA. We demonstrate that MBP causes contraction of guinea pig TSM both through stimulation of the parasympathetic nervous system and secretion of a cyclooxygenase mediator. Neither PL nor PA, while of similar molecular weight and charge as MBP, cause TSM contraction via the parasympathetic nervous system, though some cationic proteins may act via a prostanoid mediator. Thus the cationic charge of MBP is not solely responsible for its effects on TSM in the guinea pig.


1988 ◽  
Vol 66 (6) ◽  
pp. 820-825 ◽  
Author(s):  
Marian E. Addy ◽  
John F. Burka

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.


2010 ◽  
Vol 298 (5) ◽  
pp. C1118-C1126 ◽  
Author(s):  
Masaru Watanabe ◽  
Masatoshi Yumoto ◽  
Hideyuki Tanaka ◽  
Hon Hui Wang ◽  
Takeshi Katayama ◽  
...  

To explore the precise mechanisms of the inhibitory effects of blebbistatin, a potent inhibitor of myosin II, on smooth muscle contraction, we studied the blebbistatin effects on the mechanical properties and the structure of contractile filaments of skinned (cell membrane permeabilized) preparations from guinea pig taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca2+-induced tension development at any given Ca2+ concentration but had little effects on the Ca2+-induced myosin light chain phosphorylation. Blebbistatin also suppressed the 10 and 2.75 mM Mg2+-induced, “myosin light chain phosphorylation-independent” tension development at more than 10 μM. Furthermore, blebbistatin induced conformational change of smooth muscle myosin (SMM) and disrupted arrangement of SMM and thin filaments, resulting in inhibition of actin-SMM interaction irrespective of activation with Ca2+. In addition, blebbistatin partially inhibited Mg2+-ATPase activity of native actomyosin from guinea pig taenia cecum at around 10 μM. These results suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent.


1986 ◽  
Vol 8 (8) ◽  
pp. 67
Author(s):  
Ana Maria Chagas ◽  
Zuleica Tabarelli ◽  
Ruben Boelter ◽  
Lisandre Kipper ◽  
Rejane Mello Flores ◽  
...  

Animals poisoning by ingestion of Ramaria flava brunnescens fungus found in Eucalipto groves is common in Southern Brazil. This poisoning does not have an effective antidote yet and it is common to avoid the toxicity by removing the animals from these fields or by using atropin when fungus intoxication signals appear. Present work was reallized to elucidate the manner and place of action of this fungus aqueous extract on isolated guinea pig ileum. For this purpose, we used Magnus Bath and strain transducer to Physiograph connect. Experiences were realized with 18 ileum tested with 10 mcg Nicotine. 24.600 mcg Ramaria flavo brunnescens fungus' aqueous extract and 30 mcg Hexametonium. Those concentrations were choosen from pilot experiences. The results showed that uses of this fungus extract provokes smooth muscle contraction similar to that of nicotin, the difference between both occurs due to Hexametone blockade impossibility. This fact suggests that the death mechanism of animals that eat this fungus is not due to ganglionar stimulation.


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