Discrimination by benextramine between the NPY‐Y1 receptor subtypes present in rabbit isolated vas deferens and saphenous vein

• Published in: British journal of pharmacology Vol. 115; no. 1; pp. 3 - 10
• Main Authors: Palea, S., Corsi, M., Rimland, J.M., Trist, D.G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1995; Nature Publishing
• Subjects: [Leu31, Pro34] NPY; Animals; benextramine; Biological and medical sciences; Blood vessels and receptors; Culture Techniques; Cystamine - analogs & derivatives; Cystamine - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Male; Neuropeptide Y - pharmacology; NPY18‐3; Peptides - pharmacology; Rabbit isolated vas deferens and saphenous vein; Rabbits; receptor inactivation methods; Receptors, Neuropeptide Y - classification; Receptors, Neuropeptide Y - drug effects; Receptors, Neuropeptide Y - metabolism; Saphenous Vein - drug effects; Saphenous Vein - metabolism; Vas Deferens - drug effects; Vas Deferens - metabolism; Vertebrates: cardiovascular system; Neuropeptide Y; Peptide hormone; Rabbit; Smooth muscle; Lagomorpha; Male genital system; In vitro; Vas deferens; Vertebrata; Mammalia; Saphenous vein; Blood vessel; Circulatory system; Hormonal receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1995.tb16311.x

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, [Leu31Pro34] 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 = NPYl8‐36. Incubation with benextramine (BXT) at 100 μM for 30min irreversibly abolished the contractile response to [Leu31, Pro34] NPY but was ineffective against NPY18‐3‐induced contractions. 3 Cumulative dose‐response curves to [Leu31, Pro34] NPY were performed in the same preparation before and after incubation with 100 μM BXT for 20 min in order to inactivate NPY Y1 receptors. The pKA (‐logATA) 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>[Leu3l, Pro34] NPY ≥ NPY ≥ hPP>NPY2–36gGt;NPY13–36≫NPY18–36 which indicates the presence of a prejunctional NPY Y1 receptor. BXT at 100 μM incubated for 10 or 60 min did not antagonize the response to [Leu3l, 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 prejunctional NPY Y1 receptor subtype which is not blocked by BXT. Tetramine disulphides such as BXT could be useful tools in classifying NPY receptors.