On the terminal part of the guinea-pig ileum GABA produces contraction whereas on the preterminal it produces an initial short-lasting contraction followed by a prolonged relaxation. The increasing range of concentrations of GABA produces a concentration-dependent decrease in contractions and an increase in contractions of the preterminal ileum. Both contractions and relaxations can be blocked by atropine, indicating the cholinergic nature of the responses. These effects are due to the action on GABAA receptors. Depending on the duration of the incubation period (3 and 60 sec) GABA produced either potentiation or depression of the contractile effects of acetylcholine on the ileum. All the three neurotoxic insecticides (lindan malathion, permethrine) affect the contractile effects of acetylcholine on the ileum. Lindan and permetrine antagonized the contractile effects of acetylcholine, whereas malathion produced a potentiation. Malathion significantly depressed the contractile effects of the electrical field stimulation of the ileum. This effect is probably realized through the local release of GABA. Both lindan and permethrine were found to decrease the duration of the barbiturate sleeping time, whereas malathion significantly prolonged its duration. The action of lindan and permethrine is presumably realized by blocking or interfering with the function of GABAA receptors. Malathion is an anticholinesterase, thus producing an accumulation of acetylcholine at the critical sites, consequently producing a prolongation of the barbiturate sleeping time. In conclusion, neurotoxic insecticides (lindan, permethrine, malathion) affect both central and peripheral GABA-ergic systems. They can produce either depression or stimulation of these systems. They also highly significantly modulate the activity of the cholinergic system in the isolated guinea-pig ileum

Malathion by itself produced a double-phased blood pressure response in the anaesthetized rat. Immediately after intravenous injection of malathion there was a shortlasting hypotension (up to 90 sec), followed by a prolonged hypertension similar to that observed after intravenous injection of phisostigmine to rats. The hypotensive response is probably due to accumulation of acetylcholine after cholinesterase inhibition by malathion. The hypertensive response to malathion is due to secondary activation of adrenergic mechanisms in the central nervous system. Malathion coused dose-dependent inhibition of the central cholinergically mediated hypertension in rats produced by intravenous injection of physostigmine. Both the degree and duration of hypertension were equally depressed. These experiments indicate that development of central cholinergically-mediated hypertension is possible only in the presence of functionally competent cholinesterase. Both lindan and permethrine also depress the central cholinergically mediated hypertension produced by intravenous injection of physostigmine. Thus, all the three neurotoxic insecticides can inhibit transmitter interaction which is the basis of central cholinergically mediated hypertension, but not necessarily by the same mechanisms

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