Release of Histamine and Formation of Slow Reacting Substance in the Cat Paw Induced by Compound 48/80

Abstract

A method for perfusion of cat paws with constant flow and temperature is described. This technique has been used to study the relationship between the efflux of histamine and slow reacting substance (SRS) from cat paws perfused with compound 48/80. The threshold dose of compound 48/80 was 0.001–0.01 μg/ml for both histamine and SRS releasing effects. No correlation between the yields of histamine and SRS was noted. On repeated administration of compound 48/80 the histamine releasing effect declined and the output of SRS was cor respondingly reduced. The release of histamine and the formation of SRS were inhibited by ninhydrin, N‐ethylmaleimide and potassium cyanide indicating that both processes are dependent on energy‐requiring enzymatic reactions. Apart from their antagonism of the histamine releasing effect of compound 48/80, ninhydrin and N‐ethylmaleimide released histamine per se. No SRS was detected in the effluents from paws perfused with these agents alone. The yields of both histamine and SRS were higher at 22o C than at 37oC. Regardless of temperature the efflux of histamine consistently preceded that of SRS. A temperature dependent inactivation of SRS by cat serum was demonstrated. The results suggest that the initial reaction(s) activated by compound 48/80 is common for the release of histamine and the formation of SRS in the cat paw but that these processes then proceed independently.

Inhibition of Histamine Release and Formation of Slow Reacting Substance by Polyphloretin Phosphate

“…The present results show that polyphloretin phosphate (PPP) can inhibit histamine release induced by compound 48/80, bee venom and antigen. In the tissues studied, these agents initiate release process(es) by activating 1967;STRANDBERG 1971). On the other hand, PPP had no effect on histamine release from rat mast cells induced by chlorpromazine or n-decylamine.…”

Monkey SRS-A

“…The immunological release of SRS-A from monkey skin was not unexpected. Thus, antigen-induced re lease of SRS-A from guinea pig skin [6], as well as the non-immunological release of SRS from cat skin by compound 48/80 have already been described [25], Most tissues found to release histamine also release SRS-A [3,4,6,12,22,24,25]. Similarly, rat mast cells and polymor phonuclear leucocytes release both mediators under appropriate immu nological conditions [20,21].…”

Vascular effects of slow reacting substance (SRS) in the cat nasal mucosa and the appearance of a SRS‐like principle in cat nasal secretion on nerve stimulation

“…The SRS used in this study was obtained from cat paws perfused with a modified Tyrode solution containing the histamine releasing agent compound 48/80 (Strandberg 1971). After centrifugation to remove cells (350xg.…”

“…The bioactivity of the material eluted and the secretion obtained on stimulation of the Vidian nerve were analyzed by bioassay on the atropinized and mepyraminized isolated guinea pig ileum as described previously (Strandberg 1971). One unit of SRS is defined as the average threshold response to SRS on this preparation under standardized conditions (Strandberg 1971).…”