Abstract
We investigated whether or not surgical denervation of the rat vas deferens changes the α1-adrenoceptor subtypes involved in the contractions to noradrenaline. Denervated vas deferens was ≈22 times more sensitive to noradrenaline (pD2=7.35±0.04) than control vas (pD2=6.01±0.03). This difference in noradrenaline potency was eliminated when cocaine (6 μM) was added to control vas (pD2=7.22±0.04). The noradrenaline-induced contractions of control and denervated vas deferens were insensitive to the α1B/α1D-adrenoceptor alkylating agent chloroethylclonidine (100 μM, 45 min). The concentration-response curves to noradrenaline in control and denervated vas deferens were competitively antagonised by prazosin (pA2≈9.6), WB-4101 (pA2≈9.5), 5-methyl urapidil (pA2≈8.4), phentolamine (pA2≈8.7), yohimbine (pA2≈6.9), BMY 7378 (pA2≈6.9) and indoramin (pA2≈8.7). After the treatment of control and denervated vas deferens with phenoxybenzamine, the partial agonist oxymetazoline antagonised competitively the concentration-response curves to noradrenaline showing pA2 values ≈7.4 in both groups. We conclude that noradrenaline-induced contractions in control and denervated rat vas deferens are mediated by α1A-adrenoceptors and that surgical denervation of the rat vas deferens is not able to change the α1-adrenoceptor subtypes involved in the contractions to noradrenaline.
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References
Aboud R, Shafii M, Docherty JR (1993) Investigation of the subtypes of alpha 1-adrenoceptor mediating contractions of rat aorta, vas deferens and spleen. Br J Pharmacol 109:80–87
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Burt RP, Chapple CR, Marshall I (1995) Evidence for a functional alpha 1A- (alpha 1C-) adrenoceptor mediating contraction of the rat epididymal vas deferens and an alpha 1B-adrenoceptor mediating contraction of the rat spleen. Br J Pharmacol 115:467–475
Daniels DV, Gever JR, Jasper JR, Kava MS, Lesnick JD, Meloy TD, Stepan G, Williams TJ, Clarke DE, Chang DJ, Ford A P (1999) Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies. Eur J Pharmacol 370:337–343
DeGaris RM, Pennefather JN (1987) Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy. J Auton Pharmacol 7:267–279
Docherty JR (1998) Subtypes of functional alpha1- and alpha2-adrenoceptors. Eur J Pharmacol 361:1–15
Faure C, Pimoule C, Arbilla S, Langer SZ, Graham D (1994) Expression of alpha 1-adrenoceptor subtypes in rat tissues: implications for alpha 1-adrenoceptor classification. Eur J Pharmacol 268:141–149
Ford AP, Daniels DV, Chang DJ, Gever JR, Jasper JR, Lesnick JD, Clarke DE (1997) Pharmacological pleiotropism of the human recombinant alpha1A-adrenoceptor: implications for alpha1-adrenoceptor classification. Br J Pharmacol 121:1127–1135
Kasuya Y, Goto K, Hashimoto H, Watanabe H, Munakata H, Watanabe M (1969) Nonspecific denervation supersensitivity in the rat vas deferens "in vitro". Eur J Pharmacol 8:177–184
Laz TM, Forray C, Smith KE, Bard JA, Vaysse PJ, Branchek TA, Weinshank RL (1994) The rat homologue of the bovine alpha 1c-adrenergic receptor shows the pharmacological properties of the classical alpha 1A subtype. Mol Pharmacol 46:414–422
Michel MC, Kenny B, Schwinn DA (1995) Classification of alpha 1-adrenoceptor subtypes. Naunyn-Schmiedebergs Arch Pharmacol 352:1–10
Minneman KP, Theroux TL, Hollinger S, Han C, Esbenshade TA (1994) Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. Mol Pharmacol 46:929–936
Piascik MT, Guarino RD, Smith MS, Soltis EE, Saussy DL Jr, Perez DM (1995) The specific contribution of the novel alpha-1D adrenoceptor to the contraction of vascular smooth muscle. J Pharmacol Exp Ther 275:1583–1589
Pupo AS (1998) Functional effects of castration on alpha1-adrenoceptors in rat vas deferens. Eur J Pharmacol 351:217–223
Pupo AS, Cavenaghi DL, Campos M, Lucena Morais P, Jurkiewicz NH, Jurkiewicz A (1999) Effects of indoramin in rat vas deferens and aorta: concomitant alpha1-adrenoceptor and neuronal uptake blockade. Br J Pharmacol 127:1832–1836
Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ et al (1995) Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther 272:134–142
Stassen FR, Maas RG, Schiffers PM, Janssen GM, De Mey JG (1998) A positive and reversible relationship between adrenergic nerves and alpha-1A adrenoceptors in rat arteries. J Pharmacol Exp Ther 284:399–405
Villalobos-Molina R, Ibarra M (1996) Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes. Eur J Pharmacol 298:257–263
Zhong H, Minneman KP (1999) Alpha1-adrenoceptor subtypes. Eur J Pharmacol 375:261–276
Acknowledgements
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – Proc. No. 98/11031-2 to A.S. Pupo). M. Campos and P.L. Morais received studentships from FAPESP and CAPES, respectively.
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Campos, M., de Lucena Morais, P. & Pupo, A.S. Functional characterisation of α1-adrenoceptors in denervated rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 368, 72–78 (2003). https://doi.org/10.1007/s00210-003-0770-z
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DOI: https://doi.org/10.1007/s00210-003-0770-z