Heterogeneity of prejunctional neuropeptide Y receptors inhibiting noradrenaline overflow in the portal vein of freely moving rats.
The effects of intraportal infusions of different doses of neuropeptide Y, its selective neuropeptide Y Y1 receptor analogue, [Leu31,Pro34]neuropeptide Y, and the Y2-selective C-terminal fragment, neuropeptide Y-(18-36), on basal and electrically evoked noradrenaline overflow in the portal vein as well as on mean arterial pressure and heart rate were investigated in permanently instrumented freely moving rats. Neuropeptide Y dose dependently (2-2000 ng/kg/min) attenuated the electrically evoked noradrenaline overflow and almost complete blockade was reached at the highest dose used. [Leu31,Pro34]Neuropeptide Y also dose dependently (20-20,000 ng/kg/min) attenuated the evoked overflow, reaching a maximum of 55% inhibition at the highest dose (20,000 ng/kg/min). Neuropeptide Y-(18-36) attenuated the evoked release only at 20,000 ng/kg/min (by 46%). Only at the highest dose did neuropeptide Y (2000 ng/kg/min) and [Leu31,Pro34]neuropeptide Y (20,000 ng/kg/min) significantly enhance mean arterial pressure and decrease heart rate and basal plasma noradrenaline levels, the latter two effects being due to the baroreceptor reflex. Neuropeptide Y-(18-36) did not influence these parameters at all doses used. The results indicate the presence of prejunctional neuropeptide Y Y1 receptors, and possibly the coexistence of Y1 and Y2 receptors, in the portal vein of freely moving rats, which in conjunction are able to inhibit markedly electrically evoked noradrenaline overflow. Postjunctional neuropeptide Y receptors mediating an increase in blood pressure in the freely moving rat are solely of the Y1 subtype.
Coppes
R P
RP
Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, Netherlands.
Smit
J
J
Geurtsen
A M
AM
Roffel
A F
AF
Dahlöf
C
C
Doods
H N
HN
Zaagsma
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D005768:Gastrointestinal Hormones / Q000378:metabolism / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000187:drug effects / Q000502:physiology*
D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D009638:Norepinephrine