Sensitization of adenylate cyclase by short-term activation of 5-HT1A receptors

Cell Signal. 2003 Dec;15(12):1111-7. doi: 10.1016/s0898-6568(03)00115-3.

Abstract

Long-term (18 h) activation of 5-HT1A receptors alters 5-HT1A receptor-G protein coupling and leads to heterologous sensitization of adenylate cyclase. In contrast, the effects of short-term (2 h) 5-HT1A receptor activation on subsequent adenylate cyclase activity have not been determined. The present study examined and characterized 5-HT1A receptor-induced heterologous sensitization following short-term activation in CHO-5-HT1A cells. Short-term activation of 5-HT1A receptors with full agonists, as well as the partial agonist, buspirone, markedly enhanced subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization was evident after 30 min treatment with 5HT and appeared to be near maximal following 2 h agonist treatment. Sensitization was characterized by a dose-dependent increase in forskolin-stimulated cyclic AMP accumulation and was prevented by WAY 100635 or by pertussis toxin treatment. The ability of the 5-HT1A agonists to induce heterologous sensitization was not significantly altered by agents shown previously to modulate 5-HT1A-mediated inhibition of cyclic AMP accumulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Arachidonic Acid / pharmacology
  • Buspirone / pharmacology
  • CHO Cells
  • Calcimycin / pharmacology
  • Colforsin / pharmacology
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology
  • Humans
  • Indoles / pharmacology
  • Indomethacin / pharmacology
  • Maleimides / pharmacology
  • Pertussis Toxin / pharmacology
  • Phorbol Esters / pharmacology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Serotonin / pharmacology
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Time Factors
  • Tryptamines / pharmacology

Substances

  • Flavonoids
  • Indoles
  • Maleimides
  • Phorbol Esters
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Tryptamines
  • Receptor, Serotonin, 5-HT1A
  • LY 293284
  • Colforsin
  • phorbol-12-myristate
  • Arachidonic Acid
  • Serotonin
  • Calcimycin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cycloheximide
  • Cyclic AMP
  • Pertussis Toxin
  • Adenylyl Cyclases
  • bisindolylmaleimide
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Buspirone
  • Indomethacin