Cholinergic Neurotransmission and Toxicity – Neonicotinoids and Spinosad

Abstract

Neonicotinoid insecticides are chemically similar to nicotine, exerting their activity by acting as agonists of the nicotinic acetylcholine receptor (nAChR). nAChRs are polypeptides consisting of five subunits arranged around a central non-selective cation channel and are located at the neuromuscular junction, in the autonomic ganglia and in the brain. Activation of the receptor following neonicotinoid binding allows the transit of ions, including sodium, potassium and calcium. Differences in the receptor subunit composition underlie the basis for the selective activity of the neonicotinoids on insects compared to mammalian nAChRs. The insecticidal mode of action causes prolonged excitation of neuronal cell membranes, leading to paralysis and cell energy exhaustion. In contrast, neonicotinoids exhibit relatively low mammalian toxicity. Spinosad is a naturally occurring macrocyclic lactone insecticide, manufactured as a fermentation product of the soil organism Saccharopolyspora spinosa. The insecticidal activity of spinosad is due to the components spinosyn A and spinosyn D, which account for approximately 88% of the fermentation product and are present in a ratio of 6 : 1 or 7 : 1. The spinosyns cause persistent activation of insect nAChRs, resulting in widespread excitation of neurons in the insect central nervous system, involuntary muscle contractions and tremors. Spinosad is also selectively toxic to insects, showing no clear evidence of neurotoxicity in mammals.