Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the nature of the antigen-antibody complexes which initiate the specific wheal-and-flare (W & F) reaction in sensitized man, a homologous series of bivalent, oligovalent, and multivalent benzylpenicilloyl (BPO) haptens were quantitatively compared for their effectiveness in eliciting W & F in BPO-sensitized human subjects.A series of seven divalent haptens were capable of eliciting W & F, but these generally were not maximally effective elicitors. Of the divalent haptens, those with separation chains of 8 or 13 A were the most effective. Of the oligovalent haptens, maximal effectiveness was attained with BPO(6)-lysine(7), and not with BPO(2)-lysine(3) or BPO(4)-lysine(4), i.e., haptens which are 6- 3- and 4-valent, respectively, from a chemical point of view. However, evidence was obtained from quantitative precipitation experiments which indicated that BPO(6)-lysine(7) functions as a trivalent hapten immunologically, i.e., capable of binding three antibody molecules per mole hapten. Large molecularsized haptens with immunological valences of 7 or 12, but in which the haptenic groups were widely separated, were comparatively ineffective elicitors of W & F. In individual subjects, threshold W & F reactions were obtained with equimolar concentrations of the differently sized divalent, oligovalent, and multivalent haptens. The results demonstrate that for maximally effective elicitation of W & F by haptens, trivalency with optimal distances of separation of haptenic groups is necessary and sufficient. These results indicate the requirement for the formation of a high energy complex of two or three membrane-fixed skin-sensitizing antibody molecules closely bridged together by the elicitor hapten as the initiator of the W & F reaction.
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PMID:The nature of the antigen-antibody complexes initiating the specific wheal-and-flare reaction in sensitized man. 563 43

Substance P (6.25-25 p-mole) produced dose-dependent flare and wheal responses when injected intradermally into the volar surface of the human forearm. The maximum flare response was obtained within the first 3 min of injection and declined thereafter. The wheal response reached a maximum after 12 min following the injection. Only those peptides having one or more basic residues in the N-terminal region were effective in producing a flare reaction. Eledoisin-related peptide and SP1-9 were 17 and 7 times less active than substance P respectively, whilst [D-pro2, D-phe7, D-trp9]SP1-11 was twice as active. The N-terminal tetrapeptide, SP1-4 and eledoisin were inactive in the dose range tested. Wheal-producing activity was not dependent on the presence of basic residues and the rank order of relative potencies was: physalaemin (2.0): [D-pro2, D-phe7, D-trp9]SP1-11 (1.1): SP1-11 (1.0): SP4-11 (0.4): SP1-9 (0.15): eledoisin-related peptide (0.08): eledoisin (0.06). The N-terminal tetrapeptide failed to produce a wheal response in the dose range tested. Substance P was approximately equi-active with poly-L-arginine in the production of wheal and flare and both of these agents were about 10 times more potent than histamine. Adenosine triphosphate (25-400 n-mole) produced dose-dependent wheal and flare responses and was 10,000 times less potent than substance P. Pre-treatment of the subjects with the H1 histamine antagonist, chlorpheniramine, (20 mg I.V.) reduced the wheal and flare responses to substance P. Local anaesthetic injection into the skin reduced the spread of the flare response but did not affect the development of the wheal response. Pre-treatment of the skin with capsaicin reduced the flare but not the wheal response to intradermal injection of histamine. The results are discussed in relation to the mechanism of the 'axon reflex' vasodilatation in skin. This is thought to involve mast cells in addition to substance P-containing primary afferent neurones.
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PMID:Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. 619 37