NK-1 receptor mediation of neurogenic plasma extravasation in rat skin.
1. Plasma extravasation was induced by electrical nerve stimulation and by perfusion of tachykinins over a vacuum-induced blister base on rat footpad. 2. Stimulation of the sciatic nerve (18 V, 15 Hz, 0.5 ms) for 20 min produced a significant increase in the protein content of the perfusate. The response in capsaicin pretreated rats was only 4% of the control response. This indicates that the electrically-induced plasma extravasation response was mediated by capsaicin-sensitive sensory fibres. 3. Exogenous perfusion of the mammalian tachykinins substance P, neurokinin A and neurokinin B and the non-mammalian tachykinins physalaemin, kassinin and eledoisin was used to determine the tachykinin receptor type mediating the plasma extravasation response. Dose-response curves of the tachykinins (10(-9) M-10(-4) M) gave a rank order of potency of substance P = physalaemin greater than eledoisin greater than or equal to kassinin greater than neurokinin B = neurokinin A. 4. In addition, specific agonists of neurokinin receptors were perfused. Perfusion of [Glp6, D-Pro9] SP6-11 and [Glp6, L-Pro9]SP6-11 demonstrated that the L-Pro isomer was much more potent than the D-Pro isomer. 5. The rank order of potency and the greater potency of [Glp6, L-Pro9]SP6-11 over its D-isomer indicate an NK-1 neurokinin receptor mediates plasma extravasation in rat footpad skin.
Andrews
P V
PV
National Research Institute of Gerontology and Geriatric Medicine, Mount Royal Hospital, Parkville, Australia.
Helme
R D
RD
Thomas
K L
KL
D000818:Animals; D001768:Blister / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004600:Eledoisin / Q000494:pharmacology; D015286:Kassinin / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D010803:Physalaemin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D010803:Physalaemin; D013373:Substance P; D015286:Kassinin; D004600:Eledoisin; D015288:Neurokinin A