Table 2.
Experimental evidence of OP-induced muscarinic receptor dysfunction
| OP | Model | Exposure Paradigm | Key Findings | Reference |
|---|---|---|---|---|
| Sarin | Rat | Inhalation, 0.2 or 0.4 mg/m3 for 1 h/day; 1, 5, or 10 days | ↓M1 and M3 receptor densities in multiple brain regions when exposed during heat stress | (103) |
| CPF/CPO | Neonatal rat | Oral 1.5 or 3 mg·kg−1·day−1 CPF, 0.25 or 0.35 mg·kg−1·day−1 CPO; PND 1–6 | ↓Forebrain mAChR density by CPF but not CPO | (18, 19) |
| CPF | Guinea pig | sc, 70 or 390 mg/kg | ↑AHR via neuronal M2 receptor dysfunction | (83) |
| PTH, DZN | Guinea pig | sc, 1–10 mg/kg PTH, 0.75–75 mg/kg DZN | ↑AHR via neuronal M2 receptor dysfunction | (141) |
| CPF/CPO, PTH/PO | In vitro protein preparation | CPO IC50 70 µM | ↓GRK2 phosphorylation of M2 by CPF/CPO but not PTH/PO | (256) |
| CPO | Primary neuronal cell culture | 100 µM | ↑Agonist-stimulated M2 internalization | (225) |
AHR, airway hyperreactivity; CPF, chlorpyrifos; CPO, chlorpyrifos-oxon; DZN, diazinon; GRK2, G protein-coupled receptor kinase-2; mAChR, muscarinic acetylcholine receptor; OP, organophosphorus pesticide; PO, paraoxon; PND, postnatal day; PTH, parathion.