Skip to main content
SpringerLink
Log in

Inhibition of presynaptic alpha-2-adrenoceptor and opioid receptor agonist responses in the rat vas deferens by chronic imipramine treatment

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The effects of chronic imipramine administration on agonist responses in rat isolated smooth muscle preparations were investigated. The administration of 20 mg/kg imipramine two times a day for 4 and 11 days resulted in an equivalent subsensitivity (approximately 8-fold) of clonidine-induced inhibition of electrically evoked contractions in the rat vas deferens (presynaptic α2-adrenoceptor response). Imipramine (4 days) resulted in a marked inhibition of the ability of [d-Ala2, d-Leu5] enkephalin to decrease electrically evoked contractions of the vas deferens (presynaptic opioid receptor response) but did not significantly affect the carbachol-induced increase in electrically evoked contractions (muscarinic receptor response). In the absence of cocaine the contractile effects of norepinephrine and tyramine in the vas deferens were, respectively, potentiated and inhibited, following imipramine (4 days), suggesting a decrease in the activity of the neuronal uptake mechanism. When determined in the presence of cocaine, the potency of the postsynaptic effects of norepinephrine in the vas deferens (α1-adrenoceptor response) was not significantly altered by imipramine (4 days). With regard to other postsynaptic receptors, imipramine (4 days) decreased slightly the potency of phenylephrine in the aorta (α1-adrenoceptor response) and increased slightly the potency of carbachol in the trachea (muscarinic receptor response) and the potency of serotonin in the rat aorta (5HT2-receptor response). Thus, chronic imipramine administration decreased the potency of presynaptic α2- and opioid agonist responses in the vas deferens but caused very little or no changes in the potencies of agonists at postsynaptic sites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abel PW, Johnson RD, Martin TJ, Minneman KP (1985) Sympathetic denervation does not alter the density or properties of alpha-1 adrenergic receptors in the rat vas deferens. J Pharmacol Exp Ther 233:570–577

    Google Scholar 

  • Ambache N, Dunk LP, Verney J, Zar MA (1972) Inhibition of postganglionic motor transmission in vas deferens by indirectly acting sympathomimetic drugs. J Physiol 227:433–456

    Google Scholar 

  • Andrade R, Aghajanian GK (1985) Opiate- and α2-adrenoceptor-induced hyperpolarization of locus ceruleus neurons in brain slices: Reversal by cyclic adenosine 3′:5′-monophosphate analogues. J Neurosci 5:2359–2364

    Google Scholar 

  • Banerjee SP, Kung LS, Riggi SJ, Chanda SK (1977) Development of β-adrenergic receptor subsensitivity by antidepressants. Nature 268:455–456

    Google Scholar 

  • Baraldi M, Poggioli R, Santi M, Vergoni AV, Bertolini A (1983) Antidepressants and opiate interactions: Pharmacological and biochemical evidences. Pharmacol Res Comm 15:843–857

    Google Scholar 

  • Barbaccia ML, Gandolfi O, Chuang D, Costa E (1983) Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites. Proc Natl Acad Sci USA 80:5134–5138

    Google Scholar 

  • Chapleo CB, Doxey JC, Myers PL, Roach AG (1981) RX 781094 a new potent, selective antagonist of α2-adrenoceptors. Br J Pharmacol 74:842P

  • Creese I, Sibley DR (1981) Receptor adaptations to centrally acting drugs. Annu Rev Pharmacol Toxicol 21:357–391

    Google Scholar 

  • Crews FT, Paul SM, Goodwin FK (1981) Acceleration of β-receptor desensitization in combined administration of antidepressants and phenoxybenzamine. Nature 290:787–789

    Google Scholar 

  • Crews FT, Smith CB (1978) Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment. Science 202:322–324

    Google Scholar 

  • Crews FT, Smith CB (1980) Potentiation of responses to adrenergic nerve stimulation in isolated rat atria during chronic tricyclic antidepressant administration. J Pharmacol Exp Ther 215:143–149

    Google Scholar 

  • Doxey JC, Roach AG (1980) Presynaptic α-adrenoceptors: In vitro methods and preparations utilized in the evaluation of agonists and antagonists. J Auton Pharmacol 1:73–99

    Google Scholar 

  • Doxey JC, Lane AC, Roach AG, Virdee NK (1984) Comparison of the α-adrenoceptors antagonist profiles of idazoxan (RX 781094), yohimbine, rauwolscine and corynanthine. Naunyn-Schmiedeberg's Arch Pharmacol 325:136–144

    Google Scholar 

  • Finberg JPM, Tal A (1985) Reduced peripheral presynaptic adrenoceptor sensitivity following chronic antidepressant treatment in rats. Br J Pharmacol 84:609–617

    Google Scholar 

  • Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Catecholamines. Springer, Berlin Heidelberg New York, pp 283–335

    Google Scholar 

  • Furchgott RF, Kirpekar SM, Rieker M, Schwab A (1963) Actions and interactions of norepinephrine, tyramine and cocaine on aortic strips of rabbit and left atria of guinea pig and cat. J Pharmacol Exp Ther 142:39–58

    Google Scholar 

  • Hong KW, Rhim BY, Lee WS (1986) Enhancement of central and peripheral α1-adrenoceptor sensitivity and reduction of α2-adrenoceptor sensitivity following chronic imipramine treatment in rats. Eur J Pharmacol 120:275–283

    Google Scholar 

  • Huidobro F, Huidobro-Toro JP, Miranda H (1980) Interaction between morphine and the opioid-like peptides in the rat vas deferens. Br J Pharmacol 70:519–525

    Google Scholar 

  • Johnson RW, Resine T, Spotnitz S, Weich N, Ursillo R, Yamamura HI (1980) Effects of desipramine and yohimbine on α2- and β-adrenoceptor sensitivity. Eur J Pharmacol 67:123–127

    Google Scholar 

  • Keith RA, Howe BB, Salama AI (1985) The modulation of peripheral β1- and α2-receptor sensitivities by the administration of the tricyclic antidepressant, imipramine, alone and in combination with α2-antagonists to rats. J Pharmacol Exp Ther 236:356–363

    Google Scholar 

  • Keith RA, Howe BB, Lindstrom DD, Do ML, Salama AI (1984) Adaptive changes in peripheral β-receptor function by the co-administration of α2-antagonists and imipramine. The Pharmacologist 26:174

    Google Scholar 

  • Kenakin TP (1980) On the importance of agonist concentration-gradients within isolated tissues. Increased maximal responses of rat vas deferentia to (−)-noradrenaline after blockade of neuronal uptake. J Pharm Pharmacol 32:833–838

    Google Scholar 

  • Kinnier WJ, Chuang DM, Costa E (1980) Down regulation of dehydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine. Eur J Pharmacol 67:289–294

    Google Scholar 

  • Langer ST (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362

    Google Scholar 

  • Lee C-M (1985) Potentiation by cholinergic agonists of contractions to field stimulation of rat vas deferens. Br J Pharmacol 86: 671–676

    Google Scholar 

  • Lemaire S, Magnan J, Regoli D (1978) Rat vas deferens: A specific bioassay for endogenous opioid peptides. Br J Pharmacol 64:327–329

    Google Scholar 

  • Liao CS, Freer RJ (1983) Acetylcholine potentiation of field stimulated rat vas deferens: A pre-synaptic muscarinic mechanism? Life Sci 33:1861 -1867

    Google Scholar 

  • Lingyuan L, Caiying Y, Zhirong Z, Ling W, Yinchang J (1986) The biphasic effects of some opiates and opioid peptides on rat vas deferens. Sci Sinica Ser B 29:864–875

    Google Scholar 

  • Lotti VJ, Chang RSL, Kling P (1981) Pre- and postsynaptic adrenergic activation by norepinephrine reuptake inhibitors in the field-stimulated rat vas deferens. Life Sci 29:633–639

    Google Scholar 

  • MacDonald A, McGrath (1980) The distribution of adrenoceptors and other drug receptors between the two ends of the rat vas deferens as revealed by selective agonists and antagonists. Br J Pharmacol 71:445–458

    Google Scholar 

  • Maggi A, U'Prichard DC, Enna SJ (1980) Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmacol 61:91–98

    Google Scholar 

  • McGrath JC (1978) Adrenergic and “non-adrenergic” components in the contractile response of the vas deferens to a single indirect stimulus. J Physiol 283:23–39

    Google Scholar 

  • McMillen BA, Warnack W, German DC, Shore PA (1980) Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha-adrenergic drugs. Eur J Pharmacol 61:239–246

    Google Scholar 

  • Miranda H, Huidobro F, Huidobro-Toro JP (1979) Evidence for morphine and morphine-like alkaloid responses resistant to naloxone blockade in the rat vas deferens. Life Sci 24:1511–1518

    Google Scholar 

  • Muscholl E (1966) Indirectly acting sympathomimetic amines. Pharmacol Rev 18:551–559

    Google Scholar 

  • Oswald I, Brezinova V, Dunleavy DLF (1972) On the slowness of action of tricyclic antidepressant drugs. Br J Psychiatry 120:673–677

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment lowers spiroperidol-labelled serotonin receptor binding. Science 210:88–90

    Google Scholar 

  • Rehavi M, Ramot O, Yavetz B, Sokolovsky M (1980) Amitriptyline Long-term treatment elevates α-adrenergic and muscarinic receptor binding in mouse brain. Brain Res 194:443–453

    Google Scholar 

  • Reisine T, Soubrie P (1982) Loss of rat cerebral cortical opiate receptors following chronic desipramine treatment. Eur J Pharmacol 77:39–44

    Google Scholar 

  • Richelson E, Nelson A (1984) Antagonism by neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther 230:94–102

    Google Scholar 

  • Richelson E, Pfenning M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: Most antidepressants selectively block norepinephrine uptake. Eur J Pharmacol 104:277–286

    Google Scholar 

  • Salama AI, Garcia A, Wang CH, Lin L, U'Prichard DC (1983a) Relationship between adaptive changes in brain α2- and β-adrenergic receptors following repeated imipramine, yohimbine and electroconvulsive shock treatment to rats. In: Usdin E, Goldstein M, Friedhoff AJ, Georgotas A (eds) Frontiers in neuropsychiatric research. MacMillan Press, London, pp 145–158

    Google Scholar 

  • Salama AI, Perry BD, Lin L, Mitrius JC, U'Prichard DC (1983b) A comparison of the α2-antagonists RX 781094 and yohimbine at central and peripheral receptors. The Pharmacologist 25:166

    Google Scholar 

  • Sarai K, Frazer A, Brunswick D, Mendels J (1978) Desmethylimipramine-induced decrease in β-adrenergic receptor binding in rat cerebral cortex. Biochem Pharmacol 27:2179–2181

    Google Scholar 

  • Scott JA, Crews FT (1982) Rapid decrease in rat brain beta adrenergic receptor binding during combined antidepressant alpha-2 antagonist treatment. J Pharmacol Exp Ther 224:640–646

    Google Scholar 

  • Smith AD (1973) Mechanisms involved in the release of noradrenaline from sympathetic nerves. Br Med Bull 29:123–129

    Google Scholar 

  • Smith CB, Garcia-Sevilla JA, Hollingsworth PJ (1981) α2-Adrenoceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment. Brain Res 210:413–418

    Google Scholar 

  • Smith CB, Hollingsworth PJ (1984) Alpha2 adrenoceptors and the mechanism of action of tricyclic antidepressant drugs. In: Fleming W, Graefe K, Langer SZ, Weiner N (eds) Neuronal and extraneuronal events in autonomic pharmacology. Raven Press, New York, pp 182–192

    Google Scholar 

  • Sneddon P, Westfall DP, Fedan JS (1982) Cotransmitters in the motor nerves of the guinea pig vas deferens: Electrophysiological evidence. Science 218:693–695

    Google Scholar 

  • Sneddon P, Westfall DP, Colby J, Fedan JS (1984) A pharmacological investigation of the biphasic nature of the contractile response of rabbit and rat vas deferens to field stimulation. Life Sci 35:1903–1912

    Google Scholar 

  • Snyder SH, Peroutka SJ (1982) A possible role of serotonin receptors in antidepressant drug action. Pharmacopsychiatry 15:131–134

    Google Scholar 

  • Sokal RA, Rohlf FJ (1969) Single classification analysis of variance. In: Biometry. WH Freeman and Company, San Francisco, pp 204–252

    Google Scholar 

  • Spyraki C, Fibiger HC (1980) Functional evidence for subsensitivity of noradrenergic alpha2-receptors after chronic desipramine treatment. Life Sci 27:1863–1867

    Google Scholar 

  • Starke K (1981) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21:7–30

    Google Scholar 

  • Sugrue MF (1981) Effects of acutely and chronically administered antidepressants on the clonidine-induced decrease in rat brain 3-methoxy-4-hydroxy-phenylethyleneglycol sulfate content. Life Sci 28:377–384

    Google Scholar 

  • Suranyi-Cadotte BE, Dam TV, Quirion R (1985) Antidepressant-anxiolytic interaction: Decreased density of benzodiazepine receptors in rat brain following chronic administration of antidepressants. Eur J Pharmacol 106:673–675

    Google Scholar 

  • Svensson TH, Usdin T (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: α-Receptor mediation. Science 202:1089–1091

    Google Scholar 

  • van Rossum JM (963) Cumulative dose-response curves. II. Techniques for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther 143:299–330

    Google Scholar 

  • Vardolov L, Pennefather JN (1976) Regional variation in the distribution of α-adrenoceptors in the vas deferens of the rat. Arch Int Pharmacodyn 221:212–222

    Google Scholar 

  • Vetulani J, Antkiewicz-Michaluk L (1985) Alpha-adrenergic receptor changes during antidepressant treatment. Acta Pharmacol Toxicol 56:55–65

    Google Scholar 

  • Vetulani J, Sulser F (1975) Action of various antidepressant pretreatments reduce reactivity of noradrenergic cyclic AMP generating system in limbic forebrain. Nature 257:495–496

    Google Scholar 

  • Vetulani J, Stawarz RJ, Dingell JV, Sulser F (1976) A possible common mechanism of action of antidepressant treatments. Reduction in the sensitivity of the noradrenergic cyclic AMP generating system in the rat limbic forebrain. Naunyn-Schmiedeberg's Arch Pharmacol 293:109–114

    Google Scholar 

  • Vetulani J, Antkiewicz-Michaluk L, Rokosz-Pelc A, Pilc A (1984) Alpha up-beta down adrenergic regulation: A possible mechanism of antidepressant treatments. Pol J Pharmacol Pharm 36:231–248

    Google Scholar 

  • Wolfe BB, Harden TK, Sporn JR, Molinoff PB (1978) Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther 207:446–457

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Stuart Pharmaceuticals, Division of ICI Americas Inc., 19897, Wilmington, DE, USA

    Richard A. Keith & Andre I. Salama

Authors
  1. Richard A. Keith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre I. Salama
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Send offprint requests to R. A. Keith at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keith, R.A., Salama, A.I. Inhibition of presynaptic alpha-2-adrenoceptor and opioid receptor agonist responses in the rat vas deferens by chronic imipramine treatment. Naunyn-Schmiedeberg's Arch Pharmacol 335, 412–419 (1987). https://doi.org/10.1007/BF00165556

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00165556

Key words

Search

Navigation