Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin.
1. The mechanisms involved in tachykinin-induced oedema were investigated in rat skin and interactions between the tachykinins and calcitonin gene-related peptide (CGRP) were studied. 2. Intradermal injections of the tachykinins, substance P, neurokinin A and neurokinin B, stimulated local oedema formation which was in each case potentiated by co-injection of the vasodilator CGRP. Oedema induced by substance P, in the presence and absence of CGRP, was significantly inhibited by pretreatment of rats with a combination of the histamine H1 antagonist, mepyramine, and the 5-hydroxytryptamine antagonist, methysergide. Oedema induced by neurokinin A or B was not inhibited by this pretreatment. 3. Intradermally-injected CGRP induced a long lasting increase in local blood flow, which was measured with a laser Doppler blood flow meter. The simultaneous injection of substance P, but not of the structurally-related neurokinins, caused a loss of the prolonged vasodilator activity of CGRP. 4. These results show that oedema induced by substance P is partially dependent on mast cell amines and that only substance P causes a loss of the prolonged vasodilator activity of CGRP. 5. We suggest that the ability of substance P to prevent the persistent vasodilator activity of CGRP may be a direct consequence of substance P-induced activation of mast cells.
Brain
S D
SD
Section of Vascular Biology, MRC Clinical Research Centre, Middlesex.
Williams
T J
TJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D004347:Drug Interactions; D004487:Edema / Q000517:prevention & control*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012212:Rheology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D006633:Histamine Antagonists; D009479:Neuropeptides; D012702:Serotonin Antagonists; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D015740:Calcitonin Gene-Related Peptide