Molecular, pharmacological, and signaling properties of octopamine receptors from honeybee (Apis mellifera) brain

G protein-coupled receptors (GPCRs) are important regulators of cellular signaling processes. Within the large family of rhodopsin-like receptors, those binding to biogenic amines form a discrete subgroup. Activation of biogenic amine receptors leads to transient changes of intracellular Ca(2+) -([Ca(2+) ]i ) or 3',5'-cyclic adenosine monophosphate ([cAMP]i ) concentrations. Both second messengers modulate cellular signaling processes and thereby contribute to long-lasting behavioral effects in an organism. In vivo pharmacology has helped reveal the functional effects of different biogenic amines in honeybees. Phenolamine octopamine has proved an important modulator of behavior. Binding of octopamine to its receptors causes elevation of [Ca(2+) ]i or [cAMP]i . To date, only one honeybee octopamine receptor that induces Ca(2+) signals has been molecularly and pharmacologically characterized. Here we examined pharmacological properties of four additional honeybee octopamine receptors. When heterologously expressed, all receptors induced cAMP production after binding to octopamine with EC50s in the nanomolar range. Receptor activity was most efficiently blocked by mianserin, a substance with antidepressant activity in vertebrates. The rank order of inhibitory potency in potential receptor antagonists was very similar on all four honeybee receptors with mianserin > cyproheptadine > metoclopramide > chlorpromazine > phentolamine. The subroot of octopamine receptors activating adenylyl cyclases is the largest that has so far been characterized in arthropods, and it should now be possible to unravel the contribution of individual receptors to the physiology and behavior of honeybees. This article is protected by copyright. All rights reserved