title: Discrimination by benextramine between the NPY-Y1 receptor subtypes present in rabbit isolated vas deferens and saphenous vein.
abstract: 1. In order to characterize the neuropeptide Y (NPY) Y1 receptors known to be present in rabbit isolated vas deferens and saphenous vein, the pharmacological activity of the selective NPY Y1 receptor agonists, [Leu31,Pro34] NPY and various other peptide agonists, together with the putative NPY antagonist, benextramine, were compared in the two tissues. 2. In rabbit isolated saphenous vein, cumulative dose-response curves to various NPY agonists were obtained. All the peptides tested caused contractions which developed quite slowly. The rank order of potency obtained was: PYY > NPY > [Leu31,Pro34] NPY = NPY2-36 > hPP >> NPY13-36 = NPY18-36. Incubation with benextramine (BXT) at 100 microM for 30 min irreversibly abolished the contractile response to [Leu31,Pro34] NPY but was ineffective against NPY18-36-induced contractions. 3. Cumulative dose-response curves to [Leu31,Pro34] NPY were performed in the same preparation before and after incubation with 100 microM BXT for 20 min in order to inactivate NPY Y1 receptors. The pKA (-logKA) estimation for [Leu31,Pro34] NPY was 7.60 +/- 0.30 using the operational model and 7.20 +/- 0.33 using the null method; the difference between the two methods was not statistically significant (P = 0.36). 4. Prostatic segments of rabbit vas deferens were electrically stimulated with single pulses. Immediately after stabilization of the contractile response, a cumulative dose-response curve to various NPY agonists was obtained in each tissue. The rank order of potency for twitch inhibition was: PYY> [Leu31,Pro34]NPY > NPY > hPP>NPY2- 36 >>NPY13-36>> NPY 18-36 which indicates the presence of a prejunctional NPY Y1 receptor. BXT at 100 microM incubated for 10 or 60 min did not antagonize the response to[Leu31,Pro34] NPY.5. We conclude that rabbit isolated saphenous vein contains a population of post-junctional NPY Y1 receptors irreversibly blocked by BXT, as well as a population of post-junctional NPY Y2 receptors,which are insensitive to BXT. In contrast, the rabbit isolated vas deferens express a pre-junctional NPYY1 receptor subtype which is not blocked by BXT. Tetramine disulphides such as BXT could be useful tools in classifying NPY receptors.
authors.affiliation: Glaxo Research Laboratories, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Palea
authors.forename: M
authors.initials: M
authors.lastname: Corsi
authors.forename: J M
authors.initials: JM
authors.lastname: Rimland
authors.forename: D G
authors.initials: DG
authors.lastname: Trist
mesh_terms: D000818:Animals; D046508:Culture Techniques; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D017476:Receptors, Neuropeptide Y / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; C029998:benextramine; D003538:Cystamine