Effects of a selective neuropeptide Y Y2 receptor antagonist, BIIE0246, on Y2 receptors at peripheral neuroeffector junctions.
1. This study investigated the effects of BIIE0246, a novel neuropeptide Y (NPY) Y2 receptor antagonist, on the inhibition of cholinergic neuroeffector transmission in rat heart and guinea-pig trachea and purinergic neuroeffector transmission in guinea-pig vas deferens produced by the NPY Y2 receptor agonist, N-acetyl [Leu28,31] NPY 24-36. 2. In pentobarbitone anaesthetized rats, supramaximal stimulation every 30 s, of the vagus nerve innervating the heart, increased pulse interval by approximately 100 ms. This response was attenuated by intravenous administration of N-acetyl [Leu28,31] NPY 24-36 (10 nmol x kg(-1)). 3. Transmural stimulation of segments of guinea-pig trachea at 1 min intervals with 5 s trains of stimuli at 0.5, 5, 10, 20 and 40 Hz evoked contractions which were reduced in force by N-acetyl [Leu28,31] NPY 24-36 (2 microM). 4. In guinea-pig vasa deferentia, the amplitude of excitatory junction potentials evoked by trains of 20 stimuli at 1 Hz was reduced in the presence of N-acetyl [Leu28,31] NPY 24-36 (1 microM). 5. In all preparations BIIE0246 attenuated the inhibitory effect of N-acetyl [Leu28,31] NPY 24-36 but had no effect when applied alone. 6. The findings support the view that the nerve terminals of postganglionic parasympathetic and sympathetic neurones possess neuropeptide Y Y2 receptors which, when activated, reduce neurotransmitter release.
Smith-White
M A
MA
Prince of Wales Medical Research Institute, Prince of Wales Hospital, Barker St., Randwick 2031, Sydney, Australia.
Hardy
T A
TA
Brock
J A
JA
Potter
E K
EK
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000502:physiology; D011687:Purines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects
D001552:Benzazepines; D011687:Purines; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246; D000109:Acetylcholine