The delta-opioid receptor in SK-N-BE human neuroblastoma cell line undergoes heterologous desensitization.
The human neuroblastoma cell line SK-N-BE expresses delta-opioid receptors negatively coupled to adenylyl cyclase. Prolonged treatment (2 h) of the cells with 100 nM etorphine leads to an almost complete desensitization (8.2 +/- 5.9 vs. 45.8 +/- 8.7% for the control). Other receptors negatively coupled to adenylyl cyclase, namely, D2-dopaminergic, alpha 2-adrenergic, and m2/m4-muscarinic, were identified by screening of these cells, and it was shown that prolonged treatment (2 h) with 1 microM 2-bromo-alpha-ergocryptine or 1 microM arterenol resulted in a marked desensitization of D2-dopaminergic and alpha 2-adrenergic receptors, respectively. Cross-desensitization experiments revealed that pretreatment with etorphine desensitized with the same efficiency the delta-opioid receptor and the D2-dopaminergic receptor, and pretreatment with 2-brorno-alpha-ergocryptine also desensitized both receptors. In contrast, pretreatment with etorphine desensitized only partly the alpha 2-adrenergic receptor response, whereas pretreatment with 1 microM arterenol partly desensitized the delta-opioid receptor response. It is concluded that the delta-opioid receptor-mediated inhibitory response of adenylyl cyclase undergoes heterolgous desensitization, and it is suggested that delta-opioid and D2-dopaminergic receptors are coupled to adenylyl cyclase via a G12 protein, whereas alpha 2-adrenergic receptor could be coupled to the enzyme via two G proteins, G12 and another member of the G1/G0 family.
Namir
N
N
Laboratoire des Neurosciences, CNRS URA 1829, Université de Caen, France.
Polastron
J
J
Allouche
S
S
Hasbi
A
A
Jauzac
P
P
D000262:Adenylyl Cyclases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D009447:Neuroblastoma; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000502:physiology*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology
D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; D017465:Receptors, Opioid, delta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases