[Mechanism of substance P-induced increase in vascular permeability in guinea pig skin].
To determine the mechanism by which substance P (SP) increases vascular permeability, we examined the potency of SP and SP fragments in inducing plasma extravasation in guinea pig skin, the effects of a histamine H1 antagonist and a muscarinic antagonist on the response, the effects of SP antagonists on the response, and the specificity of tachykinin-induced tachyphylaxis of the response. SP-induced plasma extravasation of the skin was C-terminal hexapeptide-dependent. Neither a histamine H1 antagonist nor a muscarinic antagonist inhibited the response. Two SP antagonists, which have been shown to be the most potent ones in other systems, elicited plasma extravasation in the skin by themselves, but they did not inhibit SP-induced plasma extravasation. Tachyphylaxis of SP-induced plasma extravasation was induced by intradermal preinjection of SP concentration-dependently. However, preinjection of neurokinin A or neurokinin B did not affect SP-induced plasma extravasation. We conclude that SP directly increases vascular permeability through NK-1 (SP-P) receptors in guinea pig skin.
Iwamoto
I
I
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006168:Guinea Pigs; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology*
D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P