The 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide facilitates noradrenaline release by blockade of ?2-adrenoceptors in the mouse brain cortex

Abstract

We analyzed the facilitatory effect of the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) on the electrically evoked noradrenaline release in superfused mouse brain tissue. In addition, we determined the affinities of mCPBG and two other 5-HT receptor ligands, namely 2-methyl-5-hydroxytryptamine (2-methyl-5-HT; also a 5-HT3 receptor agonist) and 5-carboxamidotryptamine (5-CT; a 5-HT1 receptor agonist) for alpha 2 binding sites. The latter two 5-HT receptor agonists were included because of the claimed involvement of alpha 2-adrenoceptors in their effects on noradrenaline release. In superfusion experiments on mouse brain cortex slices preincubated with 3H-noradrenaline, tritium overflow evoked by 2-min periods of electrical field stimulation (3 Hz) was facilitated by mCPBG and, in addition, by rauwolscine (alpha 2-adrenoceptor antagonist) and tetraethylammonium (K+ channel blocker) (which were examined for comparison). The effect of mCPBG was not affected by the 5-HT3 receptor antagonist tropisetron or by desipramine but was abolished by rauwolscine. In slices superfused with medium containing desipramine, the concentration-response curve of unlabelled noradrenaline for its inhibitory effect on the electrically (0.3 Hz) evoked overflow was shifted to the right by mCPBG and rauwolscine (apparent pA2 5.35 and 7.88, respectively). In another series of superfusion experiments, 4 electrical pulses, administered at 100 Hz, were used to evoke tritium overflow. Tritium overflow evoked by this stimulation procedure (under which an endogenous tone of noradrenaline does not develop) was not affected by mCPBG and rauwolscine but still increased by tetraethylammonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic

“…We found the binding of each radioligand to be potently inhibited by selective ligands at their respective receptors and the results closely conform to previously published data (AM‐281 –Gifford et al. , 1997; rauwolscine –Schlicker et al. , 1994; imetit –Kathmann et al.…”

Pharmacological characterization of serotonin receptor subtypes modulating primary afferent input to deep dorsal horn neurons in the neonatal rat

“…We suggest that the lower concentrations of CPBG used here preferentially activates receptors other than the 5-HT 3 receptor, and so our results using CPBG should be interpreted cautiously. For example, although CPBG is a potent high anity 5-HT 3 receptor agonist (Kilpatrick et al, 1990), it has also been shown to interact with the catecholamines, facilitating the release of noradrenaline (Schlicker et al, 1994) and inhibiting the reuptake of dopamine (Campbell et al, 1995).…”

Inhibition of NMDA-receptor mediated response in the rat medial prefrontal cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT: Intracellular studies

“…It is unlikely that the inhibitory action of 5-HT and SR 57227A in the mPFC could be indirectly mediated via activating GABAergic interneurons, as demonstrated in the hippocampus (Kawa, 1994;Piguet and Galvan, 1994;Ropert and Guy, 1991), since we have routinely included both GABA A and GABA B receptor antagonists, which completely blocked the inhibitory action of 0.5 mM GABA, in our recording medium. Alternatively, it is possible that 5-HT and SR 57227A could produce a potent inhibitory action on the NMDAinduced response by releasing DA in the mPFC, since it has been shown that 5-HT and 5-HT 3 receptor agonists increase the release of DA and other neurotransmitters in the brain (Blandina et al, 1989;Carboni et al, 1989;Chen et al, 1992;Consolo et al, 1994;Imperato and Angelucci, 1989;Jiang et al, 1990;Mongeau et al, 1994;Schlicker et al, 1994;Schmidt and Black, 1989). However, this is unlikely because the D2 agonist quinpirole exerted a limited depressant effect on NMDA-induced inward current in pyramidal cells of the mPFC, whereas the D1 agonist SKF 38393 enhanced this current (Zheng et al, 1996) and because the relatively selective D1 and D2 receptor antagonists failed to block 5-HT and 5-HT 3 agonists' depressant action on mPFC cells .…”

“…It is well known that 5-HT and 5-HT 3 receptor agonists increase the release of dopamine (DA) and other neurotransmitters in the brain (Blandina et al, 1989;Carboni et al, 1989;Chen et al, 1992;Consolo et al, 1994;Imperato and Angelucci, 1989;Jiang et al, 1990;Mongeau et al, 1994;Schlicker et al, 1994;Schmidt and Black, 1989). To ensure that 5-HT and SR 57227A did not cause the release of DA and other neurotransmitters and indirectly inhibit the NMDAevoked response in pyramidal cells of the mPFC, we performed experiments in Ca 2ϩ -free and low Ca 2ϩ (0.1 mM) plus Cd 2ϩ (0.2 mM) ACSF.…”