Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 359, Issue 6, pp 454–459

Pharmacological characterisation of 5-HT receptors positively coupled to adenylyl cyclase in the rat hippocampus

  • Rudolf Markstein
  • Machiko Matsumoto
  • Christian Kohler
  • Hiroko Togashi
  • Mitsuhiro Yoshioka
  • Daniel Hoyer
Original article

DOI: 10.1007/PL00005375

Cite this article as:
Markstein, R., Matsumoto, M., Kohler, C. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1999) 359: 454. doi:10.1007/PL00005375

Abstract

The pharmacological properties of 5-hydroxytryptamine (5-HT) receptors positively coupled to adenylyl cyclase in the rat hippocampus were investigated using selective agonists and antagonists. 5-HT (0.008–125 μM) stimulated cyclic AMP formation in homogenates of rat hippocampus in a concentration-dependent manner. The maximal increase in cyclic AMP formation occurred at 1 μM (141 ± 6%) and the half-maximal effect (EC50) at 50 ± 22 nM. Cyclic AMP accumulation induced by 1 μM 5-HT was partly inhibited by the selective 5-HT1A receptor antagonist WAY 100,635 (1 μM), the selective 5-HT4 receptor antagonist SB 203,186 (1 μM), and the 5-HT2A/C/ 5-HT7 receptor antagonist mesulergine (25 μM). WAY 100,635, SB 203,186 and mesulergine inhibited the effect of 5-HT (1 μM) by 47%, 33% and 49%, respectively. The combination of WAY 100,635 (1 μM) with SB 203,186 (1 μM) or mesulergine (25 μM) resulted in stronger inhibition than with each antagonist alone, and the combination of all three antagonists produced almost total blockade (95%) of 5-HT-induced cyclic AMP accumulation. 5-Carboxamidotryptamine (5-CT; 0.008–125 μM), a 5-HT1/5-HT7 receptor agonist, and SDZ 216–454 (0.008– 125 μM), a selective 5-HT4 receptor agonist, concentration-dependently stimulated cyclic AMP formation, but the maximal effect of each agonist was smaller than that of 5-HT alone. SDZ 216–454 (5 μM) and 5-CT (5 μM) in combination stimulated cyclic AMP formation in an additive manner. 8-OH-PIPAT and 8-OH-DPAT, two selective 5-HT1A agonists, produced a small but significant increase in cyclic AMP formation at concentrations above 0.04 μM and 10 μM, respectively. These findings suggest that at least three 5-HT receptor subtypes, i.e. 5-HT1A, 5-HT7 and 5-HT4 receptors, are involved in mediating 5-HT-induced cyclic AMP formation in rat hippocampus.

Key words Cyclic AMP5-HT1A receptor5-HT7 receptor5-HT4 receptorRat hippocampus

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Rudolf Markstein
    • 1
  • Machiko Matsumoto
    • 2
  • Christian Kohler
    • 1
  • Hiroko Togashi
    • 2
  • Mitsuhiro Yoshioka
    • 2
  • Daniel Hoyer
    • 1
  1. 1.Nervous System Research, Novartis Pharma AG, S386/746, CH-4002 Basel, Switzerland e-mail: rudolf.markstein@pharma.novartis.com, Fax: +41-61-3246458CH
  2. 2.Department of Pharmacology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, JapanJP