Abstract
Rodent vas deferens is routinely used as a native tissue preparation to assess opioid pharmacology of new compounds. The aim of this study was to investigate the effects of a selected number of opioid compounds in the human vas deferens. Stable contractions to electrical field stimulation (EFS) were inhibited by guanethidine (1 μM) and tetrodotoxin (TTX, 1 μΜ), confirming neuronally induced contractions. Contractile responses to EFS were inhibited by the selective δ-opioid agonists (DPDPE ([d-Pen2,5]enkephalin), PF-391459 (3-{4-[(R)-[(2S,5R)-4-benzyl-2,5-dimethylpiperazin-1-yl](3-hydroxyphenyl)methyl]phenyl}propanoic acid) and SNC-80 ((+)-4-[(αR)-α-((2 S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide)) (tested from 1 ρM to 10 μM or maximum), and the μ-opioid agonists DAMGO ([d-Ala2, NMe–Phe4, Gly-ol5]-enkephalin), loperamide and SC-50484 (N-{2-[(N-acetyl-l-phenylalanyl)amino]-1,1-dimethylethyl}-l-tyrosinamide). There was no effect using the selective κ agonist U50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide) (tested from 1 ρM to 10 μM). The selective δ-opioid antagonist naltrindole (10 nM) surmountably antagonised the responses to DPDPE, but not to PF-3911459. Responses to DAMGO were completely abolished in the presence of the μ-opioid antagonist CTAP (3 μM), which only weakly antagonised responses to SC-50484. We conclude that under these conditions, δ and μ-opioid receptors, but not κ-opioid receptors, are functional in the neuronally stimulated longitudinal human vas deferens. Additionally, the human vas deferens preparation can be used as part of a drug discovery screening project to assess opioid potency, efficacy and selectivity at native human tissues, thus providing more confidence in translation.
This is a preview of subscription content, log in via an institution to check access.
References
Al-Khrasani M, Spetea M, Friedmann T et al (2007) DAMGO and 6beta-glycine substituted 14-O-methyloxymorphone but not morphine show peripheral, preemptive antinociception after systemic administration in a mouse visceral pain model and high intrinsic efficacy in the isolated rat vas deferens. Brain Res Bull 74(5):369–375
Amobi N, Guillebaud J, Kaisary A et al (2003) Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens. Eur J Pharmacol 462:169–177
Anton PG, McGrath JC (1977) Further evidence for adrenergic transmission in the human vas deferens. J Physiol 273:45–55
Bigoni R, Calo G, Guerrini R et al (2001) Effects of nociceptin and endomorphin 1 on the electrically stimulated human vas deferens. Br J Clin Pharmacol 51(4):355–358
Bilsky EJ, Calderon SN, Wang T et al (1995) SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist. J Pharmacol Exp Ther 273(1):359–366
Canevari A, Pacifico P, Cugurra F et al (1986) Receptors mediating contraction of isolated human vas deferens. Pharmacol Res Commun 18:795–806
DeHaven-Hudkins DL, Burgos LC, Cassel JA et al (1999) Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther Apr 289(1):494–502
Giagnoni G, Casiraghi L, Senini R et al (1983) Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci 33(Suppl 1):315–318
Hedlund H, Andersson KE, Larsson B (1985) Effect of drugs interacting with adrenoreceptors and muscarinic receptors in the epididymal and prostatic parts of the human isolated vas deferens. J Auton Pharmacol 5:261–270
Henderson G, Hughes J, Kosterlitz HW (1972) A new example of a morphine-sensitive neuro-effector junction: adrenergic transmission in the mouse vas deferens. Br J Pharmacol 46(4):764–766
Jacobson A (1989) Minimum-structure enkephalin analogues incorporating l-tyrosine, d(or l)-phenylalanine, and a diamine spacer. J Med Chem 8:1708–1717
Matsumoto K, Takayama H, Ishikawa H et al (2005) Partial agonistic effect of 9-hydroxycorynantheidine on mu-opioid receptor in the guinea-pig ileum. Life Sci 78(19):2265–2271
Oka T, Negishi K, Suda M et al (1981) Rabbit vas deferens: a specific bioassay for opioid kappa-receptor agonists. Eur J Pharmacol 73(2-3):235–236
Portoghese PS, Sultana M, Takemori AE (1988) Naltrindole, a highly selective and potent non-peptide δ opioid receptor antagonist. Eur J Pharmacol 146(1):185–186
Smith CF, Rance MJ (1983) Opiate receptors in the rat vas deferens. Life Sci 33(Suppl 1):327–330
Steers WD (1994) Physiology of the vas deferens. World J Urol 12(5):281–285
Acknowledgments
The authors thank Dr. John Swales, Susan Mannings and Eileen Smith for their assistance in obtaining specimens.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Root, J., Wakenhut, A.M.L.C., Siggins, H. et al. Opioid receptor characterisation of neuronally stimulated isolated human vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 385, 1049–1052 (2012). https://doi.org/10.1007/s00210-012-0769-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-012-0769-4