Insect Selectivity Found in Recombinant nAChRs

Pharmacological profiles of the recombinant hybrid insect a/vertebrate yS nAChRs are poorly defined and the binding sites are not established for identified subunits versus native receptors. Functional expression of insect nAChRs of known subunit compositions facilitates understanding of the mechanism underlying these molecular interactions. However, it is difficult to heterologously express functionally robust nAChRs not only in Xenopus oocytes but also in Drosophila S2 cells [186]. Only a few functional receptors have been obtained after expression of different subunit combinations in X. oocytes or cell lines. Nevertheless, Drosophila nAChR a subunits can form homo-oligomeric functional nAChRs when coexpressed with a vertebrate pi (non-a) subunit in X. oocytes. This has been demonstrated so far for  

However, the expression of these subunits was not very effective (low amplitude-current, 5-50 nA) following application of 1 or ACh. In addition, cDNAs of Local and Loca4 from L. migratoria and Mpa5 from M. persicae have been cloned partially. 

Alternatively, all three Drosophila a. subunits (ALS, SAD, and Da2) can form functional receptors in X. oocytes when co-expressed with a chicken neuronal a4j82 subunit [197, 198], suggesting that additional insect wAChR subunits remain to be cloned. Of the hybrid receptors, the Drosophila SAD-chicken pi hybrid nAChR has been found to be highly sensitive at much lower concentrations to the 

However, other studies using recombinant nAChRs stably expressed in cell lines have demonstrated that binding of 7 and methylcarbamoylcholine to the Da3/yS2 receptor was abolished by replacing the pi with a vertebrate j84 subunit, suggesting that non-a subunits may also be important in determining sensitivity to neonicotinoids and other agonists. 

Radioligand binding studies using several M. persicae a subunits co-expressed with a rat pi subunit in the Drosophila S2 cell line also reflect pharmacological diversity in M. persicae. 

---