Biologically Active Principles Occurring on Histamine Release from Cat Paw, Guinea Pig Lung and Isolated Rat Mast Cells

Abstract

ANGGARD, E., U. BERGQVIST, B. HOGBERG, K. JOHANSSON, I. L. THON and B. UVNAS. Biologically active principles occurring on histamine release from cat paw, guinea pig lung and isolated rat mast cells. Acta physiol. scand. 1963. 59. 97-1 10. -Histamine release was induced from perfused cat paws and isolated rat mast cells with compound 48/80, and from sensitized guinea pig lungs with antigen. Concomitantly occurring biologically active substances were separated by various chromatographic procedures (silicic acid column, silicic acid impregnated paper, etc.). From all the species several spasmogenic principles were obtained. Chemical and biological properties indicated the presence of unsaturated fatty acids, phosphatidyl and phosphatidal choline and an "SRS" principle. The "SRS" principles from the three species seemed to be identical or very closely related. Phosphatidase A-like and chymotrypsin-like enzymes are present in mast cells. Such enzymes are the only enzymes shown to be able to degranulate mast cells. The possible connection between these enzymes and the formation of spasmogenic principles during histamine release is discussed. I n a series of papers we have presented evidence supporting the view that the histamine release that occurs i n the presence of compound 48/80, extracts from Cyanea a n d Ascaris (in the cat a n d rat), a n d antigens (in the guinea pig), is brought about by identical or very similar release processes in the mast cells of the three animal species UVNAS 1960, UVNAS 1961). T h e 7-633015. Acta physiol. scand. Vol. 59. 97

Biologically active substances of the mast cell

“…This principle has long been thought to occur in anaphylactic reactions only, and has consequently been called SRS-A (Brocklehurst 1963). However, recent investigations have shown that similar "slow reacting substances" occur whenever mast cells degranulate enzymatically (Anggard et al 1963).…”

“…The chemical nature of the SRS is not clear. It is not a phosphatide or a polypeptide (Anggard et al 1963), but certain experiments suggest that it may be an organic acid (Uvnas 19656).…”

“…The knowledge about the biological properties of the SRS is too incomplete to permit an evaluation of its role in the tissues. It might, however, participate in release processes in the mast cells and possibly augment and prolong the action of histamine in inflammatory and hypersensitivity reactions (Anggard et al 1963;Coombs and Gel], 1963;Uvnas 19656). On the other hand, factors within the mast cells themselves, in the serum, in the lung and in various other organs rapidly inactivate free SRS.…”

“…On the other hand, factors within the mast cells themselves, in the serum, in the lung and in various other organs rapidly inactivate free SRS. The inactivating power of the serum is, however, considerably reduced in animals sensitized to various antigens (Anggard et al 1963).…”

Sialic Acids and Slow-Reacting Substance of Anaphylaxis (SRS-A)

“…Systematic studies by Brocklehurst (7)(8)(9)(10)(11)(12), Chakrawarty et al (13)(14)(15) and other authors (1-4, 21, 24, 29) have well estab lished that, simultaneously with histamine release by specific anti gen (1-4, 7-13, 21), compound 48/80 (2,14,29) and snake venom (21,24), a substance, eliciting a characteristic contraction of the atropinized and mepyraminized guinea pig gut, is released from perfused or chopped guinea-pig lung (1-4, 7, 10-13, 15, 21), per fused human asthmatic lung (8,9), perfused cat paw (2,14,29), isolated rat mast cells (2) and other guinea pig tissues incubated in vitro (11). Owing to the characteristic latency and slow onset of contraction, the substance has been termed 'slow-reacting sub stance' (SRS) and in order to distinguish SRS released in anaphylac tic reaction from the substance (or substances) with similar pro perties liberated under other conditions, Brocklehurst (8,9) has called the former SRS-A ('slow-reacting substance of anaphylaxis').…”