RT Journal Article
SR Electronic
T1 Octopamine Receptors from the Barnacle <span class="named-content genus-species">Balanus improvisus</span> Are Activated by the α<sub>2</sub>-Adrenoceptor Agonist Medetomidine
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 237
OP 248
DO 10.1124/mol.110.063594
VO 78
IS 2
A1 Ulrika Lind
A1 Magnus Alm Rosenblad
A1 Linda Hasselberg Frank
A1 Susanna Falkbring
A1 Lars Brive
A1 Jonne M. Laurila
A1 Katariina Pohjanoksa
A1 Anne Vuorenpää
A1 Jyrki P. Kukkonen
A1 Lina Gunnarsson
A1 Mika Scheinin
A1 Lena G. E. Mårtensson Lindblad
A1 Anders Blomberg
YR 2010
UL http://molpharm.aspetjournals.org/content/78/2/237.abstract
AB G protein-coupled octopamine receptors of insects and other invertebrates represent counterparts of adrenoceptors in vertebrate animals. The α2-adrenoceptor agonist medetomidine, which is in clinical use as a veterinary sedative agent, was discovered to inhibit the settling process of barnacles, an important step in the ontogeny of this crustacean species. Settling of barnacles onto ship hulls leads to biofouling that has many harmful practical consequences, and medetomidine is currently under development as a novel type of antifouling agent. We now report that medetomidine induces hyperactivity in the barnacle larvae to disrupt the settling process. To identify the molecular targets of medetomidine, we cloned five octopamine receptors from the barnacle Balanus improvisus. We show by phylogenetic analyses that one receptor (BiOctα) belongs to the α-adrenoceptor-like subfamily, and the other four (BiOctβ-R1, BiOctβ-R2, BiOctβ-R3, and BiOctβ-R4) belong to the β-adrenoceptor-like octopamine receptor subfamily. Phylogenetic analyses also indicated that B. improvisus has a different repertoire of β-adrenoceptor-like octopamine receptors than insects. When expressed in CHO cells, the cloned receptors were activated by both octopamine and medetomidine, resulting in increased intracellular cAMP or calcium levels. Tyramine activated the receptors but with much lesser potency than octopamine. A hypothesis for receptor discrimination between tyramine and octopamine was generated from a homology three-dimensional model. The characterization of B. improvisus octopamine receptors is important for a better functional understanding of these receptors in crustaceans as well as for practical applications in development of environmentally sustainable antifouling agents.