Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor
Article first published online: 3 MAR 2010
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 159, Issue 7, pages 1450–1462, April 2010
How to Cite
Troppmann, B., Balfanz, S., Baumann, A. and Blenau, W. (2010), Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor. British Journal of Pharmacology, 159: 1450–1462. doi: 10.1111/j.1476-5381.2010.00638.x
- Issue published online: 22 MAR 2010
- Article first published online: 3 MAR 2010
- Received 29 June 2009; revised 10 November 2009; accepted 13 November 2009
- biogenic amine;
- constitutive activity;
- cellular signalling;
- G-protein-coupled receptor;
- salivary gland;
- WAY 100635
Background and purpose: 5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT1 receptor of an insect model for neurobiology, physiology and pharmacology.
Experimental approach: A cDNA encoding for the Periplaneta americana 5-HT1 receptor was amplified from brain cDNA. The receptor was stably expressed in HEK 293 cells, and the functional and pharmacological properties were determined in cAMP assays. Receptor distribution was investigated by RT-PCR and by immunocytochemistry using an affinity-purified polyclonal antiserum.
Key results: The P. americana 5-HT1 receptor (Pea5-HT1) shares pronounced sequence and functional similarity with mammalian 5-HT1 receptors. Activation with 5-HT reduced adenylyl cyclase activity in a dose-dependent manner. Pea5-HT1 was expressed as a constitutively active receptor with methiothepin acting as a neutral antagonist, and WAY 100635 as an inverse agonist. Receptor mRNA was present in various tissues including brain, salivary glands and midgut. Receptor-specific antibodies showed that the native protein was expressed in a glycosylated form in membrane samples of brain and salivary glands.
Conclusions and implications: This study marks the first pharmacological identification of an inverse agonist and a neutral antagonist at an insect 5-HT1 receptor. The results presented here should facilitate further analyses of 5-HT1 receptors in mediating central and peripheral effects of 5-HT in insects.