Histamine is an antagonist of the acetylcholine receptor at the frog endplate

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Abstract
1 The effects of histamine on the acetylcholine (ACh) receptor-channel complex were examined by means of voltage-clamp at the frog endplate. ACh was ionophoretically applied to the endplate. Histamine was added to the perfusate. 2 Histamine (100 nM − 1 mM) reversibly depressed the peak amplitude of the ACh-induced inward current in a dose-dependent manner. 3 The double reciprocal plot of the dose-response relationship between the peak ACh current and the amount of ACh applied suggested that histamine (100 μM) depressed the ACh-induced current in a competitive manner. 4 Histamine prevented the specific ACh binding site within the receptor-channel complex from binding erabutoxin, a sea-snake venom, which binds irreversibly to the specific ACh binding site. 5 Histamine had no detectable effects on the equilibrium potential of the endplate current but shortened the half-decay time of the endplate current in a voltage-dependent manner. 6 It was therefore concluded that histamine blocks not only the specific ACh binding site but also interacts with the ACh-channel site. 7 The present experiments strongly suggest that histamine can act as an antagonist to modulate nicotinic cholinergic transmission.