Modulation by 5-hydroxytryptamine of nicotinic acetylcholine responses recorded from an identified cockroach (Periplaneta americana) motoneuron

SJB Butt, Robert Maurice Pitman

Research output: Other contribution

11 Citations (Scopus)

Abstract

Recordings from the soma of the cockroach (Periplaneta americana) fast coxal depressor motoneuron (D-f) were made while acetylcholine (ACh) was regularly pressure-applied locally from a micropipette. The modulatory effects upon these nicotinic ACh responses of bath-applied 5-hydroxytryptamine (5-HT, serotonin), dopamine and octopamine were investigated under either current-clamp or voltage-clamp conditions. The biogenic amines reversibly suppressed, but never totally abolished, ACh responses, 5-HT being the most potent, with a threshold near 10(-6) m (EC50 = 5 x 10(-5) M). Occlusion experiments indicate that the amines share a common mechanism at the level of either receptors or second messenger pathways, The amines also modulated responses to nicotine or carbachol (each of which resists hydrolysis by acetylcholinesterases), indicating that the amines did not act by accelerating ACh degradation. Pharmacological antagonists were used in an attempt to characterize the receptor responsible for amine-mediated modulation. Although a number of antagonists mimicked the action of amines rather than producing blockade, the antagonistic actions of LSD and RS23597 pointed strongly to a receptor-mediated mechanism, but did not allow receptor identification. The magnitude of the modulatory effect of 5-HT was significantly reduced by intracellular guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S), indicating involvement of a G-protein. Intracellular injection of the calcium chelator BAPTA did not block the modulatory effect of 5-HT, showing that the amines do not operate through the calcium-dependent pathway by which muscarinic receptors act on nicotinic currents. The adenylate cyclase inhibitor dideoxyadenosine (DDA), on the other hand, did attenuate the action of 5-HT, suggesting involvement of cyclic AMP.

Original languageEnglish
Volume15
Publication statusPublished - Feb 2002

Keywords

  • calcium
  • cholinergic
  • G-proteins
  • serotonin
  • voltage-clamp
  • DEPENDENT PROTEIN-KINASE
  • SENSITIVE ADENYLATE-CYCLASE
  • BIOGENIC-AMINES
  • NERVOUS-SYSTEM
  • ALPHA-SUBUNIT
  • NEUROMODULATOR OCTOPAMINE
  • MEDIATED PHOSPHORYLATION
  • SYNAPTIC TRANSMISSION
  • THORACIC INTERNEURONS
  • INTRACELLULAR CALCIUM

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