An aplysia dopamine1-like receptor: molecular and functional characterization.
In Aplysia, the neurotransmitter dopamine is involved in the regulation of various physiological processes and motor functions, like feeding behaviour, and in the siphon-gill withdrawal reflex. In this paper, we report the characterization of the first Aplysia D1-like dopamine receptor (Apdop1) mainly expressed in the CNS, heart and buccal mass. Following expression of the Apdop1 receptor in HEK293 cells, a higher level of cAMP was observed in the absence of the receptor ligand, showing that Apdop1 is constitutively active. This activity was blocked by the inverse agonist flupentixol. Application of dopamine (EC50 of 35 nm) or serotonin (EC50 of 36 microm) to Apdop1-transfected HEK293 cells further increased the level of cAMP, suggesting that the receptor is linked to the stimulatory Gs protein pathway. When expressed in cultured sensory neurons, Apdop1 immunoreactivity was observed in the cell body and neurites. Control sensory neurons responded to dopamine with a decrease in excitability mediated by a pertusis toxin-sensitive G protein. Expression of Apdop1 produced an increase in hyperpolarization in the absence of agonist and an increase in membrane excitability following stimulation by dopamine. In the presence of pertussis toxin to inhibit the Gi protein inhibitory pathway responsible for decrease in excitability mechanism, Stimulation of membrane excitability was observed. Apdop1 sensitivity to dopamine makes it a potential modulator of operant conditioning procedure.
Barbas
Demian
D
Département de biochimie, Université de Montréal, Montréal, Québec, Canada.
Zappulla
Jacques P
JP
Angers
Stéphane
S
Bouvier
Michel
M
Mohamed
Habib A
HA
Byrne
John H
JH
Castellucci
Vincent F
VF
DesGroseillers
Luc
L
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005475:Flupenthixol / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D014018:Tissue Distribution; D014162:Transfection
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D018490:Serotonin Agents; D012701:Serotonin; D000242:Cyclic AMP; D005475:Flupenthixol; D004298:Dopamine