Journal
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
Volume 146, Issue 1, Pages 9-19Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpb.2006.08.018
Keywords
central pattern generator; crustacean; G protein coupled receptor; heterologous expression; signal transduction; stomatogastric
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038770] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS38770, R01 NS038770] Funding Source: Medline
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The pyloric network is an important model system for understanding neuromodulation of rhythmic motor behaviors like breathing or walking. Dopamine (DA) differentially modulates neurons within the pyloric network. However, while the electrophysiological actions of DA have been well characterized, nothing is known about the signaling events that mediate its effects. We have begun a molecular characterization of DA receptors (DARs) in this invertebrate system. Here, we describe the cloning and characterization of the lobster D-2 receptor, D-2 alpha Pan. We found that when expressed in HEK cells, the D-2 alpha Pan receptor is activated by DA, but not other monoamines endogenous to the lobster nervous system. This receptor positively couples with cAMP through multiple Gi/o proteins via two discrete pathways: 1) a G alpha mediated inhibition of adenylyl cyclase (AC), leading to a decrease in cAMP and 2) a G beta gamma-mediated activation of phospholipase beta (PLC beta), leading to an increase in cAMP. Alternate splicing alters the potency and efficacy of the receptor, but does not affect monoamine specificity. Finally, we show that arthropod D-2 receptor coupling with cAMP varies with the cellular milieu. (c) 2006 Elsevier Inc. All rights reserved.
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