Neuropeptide Y Y2 receptor-mediated attenuation of neurogenic plasma extravasation acting through pertussis toxin-sensitive mechanisms.
1. The effects of neuropeptide Y (NPY) receptor agonists (administered intravenously) were examined on plasma protein ([125I]-bovine serum albumin) leakage within dura mater evoked by unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min), capsaicin (1 mumol kg-1, i.v.) or substance P (1 nmol kg-1, i.v.) in anaesthetized Sprague-Dawley rats. 2. NPY (EC50: 5.6 nmol kg-1) and NPY fragment 13-36 [NPY (13-36)] (ED50: 4.3 nmol kg-1), an NPY Y2 receptor agonist, dose-dependently attenuated [125I]-bovine serum albumin extravasation from meningeal vessels when administered 10 min prior to electrical stimulation. [Leu31, Pro34]-NPY, an NPY Y1 and Y3 receptor agonist, inhibited the response at a higher dose only (23 nmol kg-1) (P < 0.05). 3. NPY also significantly decreased plasma protein extravasation induced by capsaicin (1 mumol kg-1) but not by substance P (1 nmol kg-1). 4. Pertussis toxin (20 micrograms kg-1, administered intracisternally 48 h prior to stimulation) blocked completely the inhibitory effect of NPY and NPY (13-36) but did not inhibit extravasation alone. 5. We conclude that NPY inhibits neurogenically-mediated plasma protein extravasation acting through presynaptic pertussis toxin-sensitive NPY Y2 receptors, possibly by inhibition of neuropeptide release from perivascular trigeminovascular afferents.
Yu
X J
XJ
Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Moskowitz
M A
MA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004388:Dura Mater / Q000098:blood supply* / Q000502:physiology; D004558:Electric Stimulation; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000188:drug therapy; D007457:Iodine Radioisotopes; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D010566:Virulence Factors, Bordetella; C095889:neuropeptide Y2 receptor; C059889:neuropeptide Y (18-36); D012710:Serum Albumin, Bovine; D013373:Substance P; D037342:Pertussis Toxin; D002211:Capsaicin