An acute inflammation induced by inorganic pyrophosphate and adenosine triphosphate, and its inhibition by cyclic 3′,5′-adenosine monophosphate

Abstract

A subcutaneous injection of inorganic pyrophosphate (PP 1) produced characteristic inflammatory lesions on rat skins, and the rats displayed acute pain reactions at the time of administration. The increase in vascular permeability due to this PP 1-induced inflammation was immediate and monophasic with no delayed response. Furthermore, this vascular response was synchronized with an increase in cutaneous histamine, indicating that PP 1-induced inflammation was mediated by endogenous histamine. ATP showed similar and more potent effects than PP 1 on changes in vascular permeability and cutaneous histamine without causing acute pain reactions. Both the vascular response and histamine release elicited by PP 1 were inhibited by simultaneous administration of epinephrine, methylxanthines and by cyclic 3',5'-adenosine monophosphate (cAMP), but not by any other adenine nucleotide or cyclic nucleoside monophosphate, except for 5'-AMP, which inhibited the increase in cutaneous histamine. cAMP was also effective in inhibiting both effects induced by ATP, while 5'-AMP suppressed only the increase in cutaneous histamine induced by ATP. PP 1 released histamine from isolated mast cells, but did not significantly release it from leukocytes. The release of histamine from mast cells induced by PP 1 as well as by ATP and compound 48 80 was also inhibited by cAMP and 5'-AMP.