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 recep tors negatively coupled to adenylyl cyclase. Prolonged treatment (2 h) of the cells with 100 nM etorphine leads to an almost complete desens itization (8.2 +/- 5.9 vs. 45.8 +/- 8.7% for the control). Other recep tors negatively coupled to adenylyl cyclase, namely, D2-dopaminergic, alpha(2)-adrenergic, and m2/m4-muscarinic, were identified by screenin g of these cells, and it was shown that prolonged treatment (2 h) with 1 mu M 2-bromo-alpha-ergocryptine or 1 mu M arterenol resulted in a m arked desensitization of D2-dopaminergic and alpha(2)-adrenergic recep tors, respectively. Cross-desensitization experiments revealed that pr etreatment with etorphine desensitized with the same efficiency the de lta-opioid receptor and the D2-dopaminergic receptor, and pretreatment with 2-bromo-alpha-ergocryptine also desensitized both receptors. In contrast, pretreatment with etorphine desensitized only partly the alp ha(2)-adrenergic receptor response, whereas pretreatment with 1 mu M a rterenol partly desensitized the S-opioid receptor response. It is con cluded that the delta-opioid receptor-mediated inhibitory response of adenylyl cyclase undergoes heterologous desensitization, and it is sug gested that delta-opioid and D2-dopaminergic receptors are coupled to adenylyl cyclase via a G(i2) protein, whereas alpha(2)-adrenergic rece ptor could be coupled to the enzyme via two G proteins, G(i2) and anot her member of the G(i)/G(o) family.