A pharmacological comparison of organophosphorus and carbamate anti-cholinesterase agents on guinea pig ileum.

The pharmacological effects of organophosphorus (4-methylthiophenyl dipropyl phosphate:propaphos, diisopropylfluorophosphate:DEP) and carbamate (physostigmine, neostigmine) anti-cholinesterase (anti-ChE) on guinea pig isolated ileum were examined. Physostigmine (0.7 or 7.2 μm) and neostigmine (0.1, 1, or 10 μm) caused a phasic and tonic contraction of the ileum, while a sustained application of propaphos (0.3, 1, 10 μm) and DFP (0.1 or 1 μm) produced intermittent contractions of slow onset. The organophosphate-induced contractions were markedly reduced by morphine (0.1 μm), tetrodotoxin (31 nm), hexamethonium (1 μm), and atropine (14 nm), which suggested a possible involvement of intrinsic cholinergic innervation in the development of its spasmogenicity. On the other hand, the carbamate-induced contraction was not significantly affected by these antagonists except atropine which inhibited it by 52.5 ± 9.8% (n = 7). The transmural stimulation- and picric acid (1 μm)-induced contractions of the ileum were significantly enhanced by lower concentrations of physostigmine (72 nm) and neostigmine (10 nm) but not by the organophosphates. Similarly, the Ca2+-induced contraction of the K+-depolarized ileum was effectively enhanced only by the carbamates. Physostigmine (7.2 μm), neostigmine (10 μm), and DFP (100 μm) did not affect the specific [3H]quinuclidinyl benzilate (QNB) binding to ileal longitudinal muscles, suggesting no direct effect of muscarinic cholinergic receptors. The acetylcholine (ACh)-induced inhibition of the [3H]QNB binding was significantly enhanced only by carbamates. Thus we conclude that organophosphates may contract guinea pig isolated ileum by an action on the intrinsic cholinergic nerves and that the carbamate-induced contraction may relate to its anti-ChE effect in cholinergic synapses as well as a direct effect on the smooth muscles.