Sequence of events in substance P-mediated plasma extravasation in rat skin.
Using a blister model of inflammation in the rat hind footpad, we have studied the temporal and quantitative contribution of mast cell mediators and prostaglandins to substance P-induced plasma extravasation. In addition substance P-related peptides (neurokinin A, SP5-11 and SP1-7) were tested for their ability to induce a plasma extravasation response and the extent of histamine involvement to the response was determined. The present results show that the plasma extravasation response to substance P consists of an early substance P-mediated response that is independent of other mediators and a late response that involves interaction between substance P, mast cell mediators and prostaglandins. An early histamine-independent response was also mediated by neurokinin A, a tachykinin that shares a common C-terminal with substance P and by a C-terminally directed analogue of substance P, namely SP5-11. On the other hand, a late histamine-dependent response was mediated by the N-terminally directed analogue, SP1-7. The present data are suggestive of a possible sequence of events that might occur during an inflammatory response to substance P and might involve independent actions of its C- and N-terminal.
Khalil
Z
Z
National Research Institute of Gerontology and Geriatric Medicine, Mount Royal Hospital, Parkville, Australia.
Helme
R D
RD
D000818:Animals; D005260:Female; D006632:Histamine / Q000378:metabolism* / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D011453:Prostaglandins; D013373:Substance P; D006632:Histamine