Spantide II, a novel tachykinin antagonist, and galanin inhibit plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw.
The effect of intradermal injection of Spantide II, a novel tachykinin antagonist, and the neuropeptide galanin on neurogenic plasma extravasation induced by antidromic stimulation of C-fibers in the sciatic nerve was examined in the hindpaws of rats. Activation of C-fibers by antidromic sciatic nerve stimulation (2 Hz, 5 min) consistently evoked a localized plasma extravasation of Evans Blue in the skin area of the hindpaw innervated by the sciatic nerve. Intradermal injection of 3 nmol Spantide II significantly inhibited this response. The plasma extravasation was nearly totally abolished when the concentration of Spantide II was increased to 9 nmol. Intradermal injection of 1.5 and 15 nmol galanin also inhibited plasma extravasation. Intradermal injection of 9 nmol Spantide II effectively blocked the plasma extravasion in the hindpaw induced by 8 nmol intravenous substance P. Plasma extravasation induced by intravenous substance P was also inhibited by the higher, but not by the lower, dose of galanin injected intradermally. The present results indicate that Spantide II, a potent non-toxic tachykinin antagonist, effectively blocks the neurogenic plasma extravasation induced by antidromic C-fiber stimulation, thus supporting the view that tachykinins play an important role in this neurogenic inflammatory process. It is further shown that galanin, a naturally occurring neuropeptide present in primary afferents, also inhibits C-fiber activation-evoked plasma extravasation, indicating an interaction between galanin and tachykinins in the peripheral terminals of primary afferents, possibly through both pre- and postsynaptic mechanisms.
Xu
X J
XJ
Department of Clinical Physiology, Karolinska Institute, Huddinge, Sweden.
Hao
J X
JX
Wiesenfeld-Hallin
Z
Z
Håkanson
R
R
Folkers
K
K
Hökfelt
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005122:Exudates and Transudates / Q000187:drug effects*; D005528:Foot / Q000098:blood supply / Q000294:innervation; D019004:Galanin; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D008969:Molecular Sequence Data; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000037:antagonists & inhibitors*
D010455:Peptides; D015320:Tachykinins; C065446:spantide II; D013373:Substance P; D019004:Galanin