Summary
The interaction of presynaptic, release-inhibiting α2-adrenoceptors, opioid κ-receptors and adenosine A1-receptors was studied in slices of the occipito-parietal cortex of the rabbit. The slices were preincubated with 3H-noradrenaline and then superfused and stimulated electrically twice for 2 min each (S1, S2). The stimulation-evoked overflow of tritium was taken to reflect action potential-evoked release of noradrenaline. One of two release-modulating compounds to be examined for interaction was kept in the medium throughout superfusion, the other one was added before S2. In many experiments, the stimulation parameters were adjusted (frequency 0.5–7 Hz; voltage drop 2–5 V/cm) in order to obtain similar reference release (S1) values despite the presence of the first release-modulating compound.
The selective κ-receptor agonist ethylketocyclazocine (EK) attenuated markedly the release-inhibiting effects of the α2-adrenoceptor-selective agonists clonidine and α-methylnoradrenaline as well as the release-facilitating effect of the α2-adrenoceptor-selective antagonist yohimbine. The attenuation occurred both when the parameters of electrical stimulation were kept constant and when they were adjusted to obtain similar S1 release values. The selective A1-receptor agonist R-N6-phenylisopropyladenosine (PIA) also attenuated the effects of clonidine and yohimbine. Conversely, clonidine attenuated and yohimbine enhanced the release-inhibiting effect of PIA. Yohimbine also enhanced the release-facilitating effect of the adenosine receptor antagonist 8-phenyltheophylline. Again, these changes occurred both at constant stimulation parameters and when stimulation parameters were adjusted. EK attenuated the release-inhibiting effect of PIA, and conversely PIA attenuated the effect of EK, both at constant and at adjusted parameters of electrical stimulation. The release-inhibiting effects of tetrodotoxin and Cd2+ remained unchanged in the presence of clonidine or EK.
These results demonstrate mutual interactions between presynaptic a2-, opioid K- and adenosine A1-receptors. As soon as any one of the three systems is activated, the inhibition due to activation of either of the two remaining systems is blunted. The interactions are not a consequence of the change in release per se that the first receptor ligand inevitably produces. α-Adrenoceptors interact with opioid κ-receptors in a similar manner, independently of the chemical nature (imidazoline or phenylethylamine derivative) of the α-agonist used. The interaction is specific for release-modulating receptors and does not extend to Na+ ar Ca2+ channel blockers. It may occur at the level of the receptors themselves or at the post-receptor transduction mechanisms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allgaier C, Hertting G, von Kügelgen O (1987) The adenosine receptor-mediated inhibition of noradrenaline release possibly involves a N-protein and is increased by α2-autoreceptor blockade. Br J Pharmacol 90:403–412
Andrade R, Aghajanian GK (1985) Opiate- and α2-adrenoceptor-induced hyperpolarizations of locus ceruleus neurons in brain slices: reversal by cyclic adenosine 3′:5′-monophosphate anatogues. J Neurosci 5:2359–2364
Chesselet MF (1984) Presynaptic regulation of neurotransmitter release in the brain. Neuroscience 12:347–375
Dubocovich ML, Langer SZ (1980) Pharmacological differentiation of presynaptic inhibitory α-adrenoceptors and opiate receptors in the cat nictitating membrane. Br J Pharmacol 70:383–393
Dubocovich ML, Weiner N (1983) Enkephalins modulate [3H]dopamine release from rabbit retina in vitro. J Pharmacol Exp Ther 224:634–639
Enero MA, Saidman BQ (1977) Possible feed-back inhibition of noradrenaline release by purine compounds. Naunyn-Schmiedeberg's Arch Pharmacol 297:39–46
Hedqvist P (1974) Prostaglandin action on noradrenaline release and mechanical responses in the stimulated guinea pig vas deferens. Acta Physiol Scand 90:86–93
Illes P (1986) Mechanisms of receptor-mediated modulation of transmitter release in noradrenergic, cholinergic and sensory neurones. Neuroscience 17:909–928
Jackisch R, Fehr R, Hertting G (1985) Adenosine: an endogenous modulator of hippocampal noradrenaline release. Neuropharmacology 24:499–507
Jackisch R, Geppert M, Illes P (1986) Characterization of opioid receptors modulating noradrenaline release in the hippocampus of the rabbit. J Neurochem 46:1802–1810
Jonzon B, Fredholm BB (1984) Adenosine receptor mediated inhibition of noradrenaline release from slices of the rat hippocampus. Life Sci 35:1571–1579
Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Limberger N, Späth L, Hölting T, Starke K (1986) Mutual interaction between presynaptic α2-adrenoceptors and opioid κ-receptors at the noradrenergic axons of rabbit brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 334:166–171
Loiacono RE, Rand MJ, Story DF (1985) Interaction between the inhibitory action of acetylcholine and the α-adrenoceptor autoinhibitory feedback system on release of [3H]-noradrenaline from rat atria and rabbit ear artery. Br J Pharmacol 84:697–705
Majewski H, Rand MJ (1981) An interaction between prejunctional α-adrenoceptors and prejunctional β-adrenoceptors. Eur J Pharmacol 69:493–498
Massingham R, Dubocovich ML, Langer SZ (1980) The role of presynaptic receptors in the cardiovascular actions of N,N-di-n-propyldopamine in the cat and dog. Naunyn-Schmiedeberg's Arch Pharmacol 314:17–28
North RA, Williams JT (1985) On the potassium conductance increased by opioids in rat locus coeruleus neurones. J Physiol (Lond) 364:265–280
Pelayo F, Dubocovich ML, Langer SZ (1980) Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of α-methylnoradrenaline on the stimulation-evoked release of 3H-noradrenaline from rat occipital cortex slices. Eur J Pharmacol 64:143–155
Ramme D, Illes P, Späth L, Starke K (1986) Blockade of α2-adrenoceptors permits the operation of otherwise silent opioid κ-receptors at the sympathetic axons of rabbit jejunal arteries. Naunyn-Schmiedeberg's Arch Pharmacol 334:48–55
Reichenbacher D, Reimann W, Starke K (1982) α-Adrenoceptor-mediated inhibition of noradrenaline release in rabbit brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 319: 71–77
Schoffelmeer ANM, Putters J, Mulder AH (1986) Activation of presynaptic α2-adrenoceptors attenuates the inhibitory effect of μ-opioid receptor agonists on noradrenaline release from brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 333:377–380
Starke K (1981) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21:7–30
Starke K (1987) Presynaptic α-autoreceptors. Rev Physiol Biochem Pharmacol 107:73–146
Taube HD, Starke K, Borowski E (1977) Presynaptic receptor systems on the noradrenergic neurones of rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 299:123–141
Vizi ES (1979) Presynaptic modulation of neurochemical transmission. Progress Neurobiol 12:181–290
Author information
Authors and Affiliations
Additional information
Send offprint requests to N. Limberger at the above address
Rights and permissions
About this article
Cite this article
Limberger, N., Späth, L. & Starke, K. Presynaptic α2-adrenoceptor, opioid κ-receptor and adenosine A1-receptor interactions on noradrenaline release in rabbit brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 338, 53–61 (1988). https://doi.org/10.1007/BF00168812
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00168812