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Evidence that 8 hydroxy 2 n dipropylaminotetralin 8 oh dpat is a selective alpha 2 adrenoceptor antagonist on guinea pig submucous neurons

, : Evidence that 8 hydroxy 2 n dipropylaminotetralin 8 oh dpat is a selective alpha 2 adrenoceptor antagonist on guinea pig submucous neurons. British Journal of Pharmacology 92(2): 341-348

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). 8-OH-DPAT (10 nM-20 .mu.M) had no direct presynaptic or postsynaptic actions on submucous plexus neurones. 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 .alpha.2-adrenceptors were 6.9-7.2. The inhibitory synaptic potential, which is due to activation of .alpha.2-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. Neuronal hyperpolarizations mediated through activation of .delta.-opioid receptors or somatostatin receptors were unaffected by 8-OH-DPAT (0.1-1 .mu.M). 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. These results suggests 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 .alpha.2-adrenoceptors.

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