The cytoskeleton as a target of antitumoral agents

Abstract

The mixed 5-HT1A/1B/1D receptor agonist 5-carboxamidotryptamine (5-CT) potently inhibited the electrically-evoked release of [3H]-5-HT in slices of human frontal cortex (70% inhibition at 30 nM), an effect blocked by 5-HT receptor antagonists with the following relative order of potency: methiothepin > metergoline = methysergide > propranolol. The selective 5-HT1A receptor agonist 8-OH-DPAT (100 nM) did not modify the evoked release of [3H]-5-HT. These results are compatible with the presence of an inhibitory 5-HT autoreceptor different from the 5-HT1A or 5-HT1B subtypes, but resembling the 5-HT1D subtype. In the rat or the guinea-pig brain, the selective 5-HT3 receptor agonist 2-methyl-5-HT enhanced in a concentration-dependent manner the electrically-evoked release of [3H]-5-HT, an effect competitively antagonized by ICS 205930 or Ondansetron, both selective 5-HT3 antagonists. Taken together, these results support the view that both presynaptic inhibitory and facilitatory 5-HT receptors can modulate 5-HT neurotransmission in brain slices, and could represent potential target sites of action for novel drugs.