Histamine is an antagonist of the acetylcholine receptor at the frog endplate.
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. Histamine (100 nM - 1 mM) reversibly depressed the peak amplitude of the ACh-induced inward current in a dose-dependent manner. The double reciprocal plot of the dose-response relationship between the peak ACh current and the amount of ACh applied suggested that histamine (100 microM) depressed the ACh-induced current in a competitive manner. 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. 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. It was therefore concluded that histamine blocks not only the specific ACh binding site but also interacts with the ACh-channel site. The present experiments strongly suggest that histamine can act as an antagonist to modulate nicotinic cholinergic transmission.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D004870:Erabutoxins / Q000037:antagonists & inhibitors; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D011898:Ranidae; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013997:Time Factors
D009498:Neurotoxins; D011950:Receptors, Cholinergic; D004870:Erabutoxins; D006632:Histamine; C032917:erabutoxin b; D000109:Acetylcholine