Octopamine receptors of the barnacle Balanus improvisus; potential targets for environmentally sustainable antifouling agents

Description of Research

Octopamine receptors of insects and other invertebrates are members of the G protein-coupled receptor superfamily and represent counterparts of the adrenoceptors in vertebrate animals. Five octopamine receptors were cloned from the barnacle Balanus improvisus. The α2-adrenoceptor agonist medetomidine, known as a veterinary sedative agent, was discovered to inhibit the settling process of barnacles by inducing hyperactivity in the barnacle larvae. On the molecular level, this effect is considered to be mediated via medetomidine-induced octopamine receptor activation. Balanus improvisus is the barnacle species causing the most severe biofouling problems in the Baltic Sea and nearby regions by settling onto ship hulls and thereby increasing fuel consumption and carbon dioxide emissions. Also other barnacle species in other regions have similar harmful effects by settling onto ship hulls, cooling water systems of power plants and seafood farming implementations.
We have developed new cell-based screening and profiling assays for octopamine receptors. Using this system, our aim is to screen chemical libraries and try to identify compounds that are able to activate octopamine receptors but not the α2-adrenoceptors of vertebrates. Vertebrate animals do not have octopamine receptors. In order to define selectivity for octopamine receptors, the binding affinity of octopamine-active compounds to the human α2-adrenoceptor subtypes will be tested in secondary screens. To improve the molecular-level understanding of the structural determinants of selectivity, molecular models of octopamine receptors will be constructed. The potential antifouling agents are also tested in vivo in collaboration with researchers at the University of Gothenburg in Sweden.

List of Personnel

Mika Scheinin, MD, PhD

Selected Publications

Lind U, Alm Rosenblad M, Hasselberg FL, Falkbring S, Brive L, Laurila JM, Pohjanoksa K, Vuorenpää A, Kukkonen JP, Gunnarsson L, Scheinin M, Mårtensson Lindblad LG, Blomberg A (2010). Octopamine receptors from the barnacle Balanus improvisus are activated by the α2-adrenoceptor agonist medetomidine. Mol Pharmacol. 78: 237-48.

Ruuskanen JO, Laurila J, Xhaard H, Rantanen VV, Vuoriluoto K, Wurster S, Marjamäki A, Vainio M, Johnson MS, Scheinin M (2005). Conserved structural, pharmacological and functional properties among the three human and five zebrafish α2-adrenergic receptors. Brit J Pharmacol. 144:165-77.

Laurila JM, Xhaard H, Ruuskanen JO, Rantanen MJ, Karlsson HK, Johnson MS, Scheinin M (2007). The second extracellular loop of α2A-adrenoceptors contributes to the binding of yohimbine analogues. Brit J Pharmacol. 151: 1293-304.

Laurila JM, Wissel G, Xhaard H, Ruuskanen J, Johnson MS, Scheinin M (2011). Involvement of the first transmembrane segment of human α2-adrenoceptors in the subtype-selective binding of chlorpromazine, spiperone and spiroxatrine. Brit J Pharmacol. 164: 1558-72.

Xhaard H, Nyrönen T, Rantanen VV, Ruuskanen JO, Laurila J, Salminen T, Scheinin M, Johnson MS (2005). Model structures of human α2-adrenoceptors in complex with automatically docked antagonist ligands raise the possibility of interactions dissimilar from agonist ligands, J Struct Biol. 150: 126-43.