Evidence that 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT) is a selective α2-adrenoceptor antagonist on guinea-pig submucous neurones
Open Access
- 1 October 1987
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 92 (2), 341-347
- https://doi.org/10.1111/j.1476-5381.1987.tb11329.x
Abstract
1 Intracellular recordings were made from neurones of the submucous plexus and from submucosal arteriolar smooth muscle of the guinea-pig ileum for the purpose of examining the actions of 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT). 2 8-OH-DPAT (10 nm-20 μm) had no direct presynaptic or postsynaptic actions on submucous plexus neurones. 3 Membrane hyperpolarizations induced in neurones by noradrenaline or UK 14304 were competitively antagonized by 8-OH-DPAT. For dose-ratios up to 40, Schild plots were linear with slopes not significantly different from unity; pA2 values for the 8-OH-DPAT antagonism of postsynaptic α2-adrenoceptors were 6.9-7.2. 4 The inhibitory synaptic potential, which is due to activation of α2-adrenoceptors located on submucous plexus neurones, was selectively inhibited by 8-OH-DPAT; the IC50 value for inhibition of the inhibitory synaptic potential was 250 nm. 5 Neuronal hyperpolarizations mediated through activation of δ-opioid receptors or somatostatin receptors were unaffected by 8-OH-DPAT (0.1–1 μm). 6 The ability of noradrenaline and UK 14304 to inhibit the release of acetylcholine at synapses in the submucous plexus, and to inhibit the release of the transmitter which mediates the excitatory junction potential in the submucosal arteriolar smooth muscle, was also blocked by 8-OH-DPAT. 7 These results suggest that some of the actions of 8-OH-DPAT previously ascribed to agonism at 5-hydroxytryptamine (5-HT)1 receptors may actually result from blockade of the actions of endogenously released noradrenaline acting on α2-adrenoceptors.This publication has 31 references indexed in Scilit:
- Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT1A and 5‐HT1B agonistsSynapse, 1987
- A G Protein Couples Serotonin and GABA B Receptors to the Same Channels in HippocampusScience, 1986
- 5-Hydroxytryptamine mediates inhibitory postsynaptic potentials in rat dorsal raphe neuronsNeuroscience Letters, 1985
- Characterization of α2-adrenoceptors which increase potassium conductance in rat locus coeruleus neuronesNeuroscience, 1985
- 5-HT1 receptor sites and functional correlatesNeuropharmacology, 1984
- Hyperpolarization of serotonergic neurons by serotonin and LSD: Studies in brain slices showing increased K+ conductanceBrain Research, 1984
- 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition siteEuropean Journal of Pharmacology, 1983
- 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activityJournal of Neural Transmission, 1982
- 8-Hydroxy-2-(dipropylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonistJournal of Medicinal Chemistry, 1981
- Regulation of noradrenaline release by presynaptic receptor systemsReviews of physiology, biochemistry and pharmacology, 1977