Acetylcholine Receptors in Small Cell Carcinomas

Abstract: The presence of muscarinic and nicotinic acetylcholine receptors (m‐ and nAChR, respectively) in small cell carcinomas (SCC) of the lung was assessed by measurement of specific binding of (—)[³H]quinuclidinyl benzilate ([³H]QNB) and ¹²⁵I‐α‐bungarotoxin, respectively. Of five SCC studied, four were originally derived from patients with the Lambert‐Eaton myasthenic syndrome, an autoimmune disease of neuromuscular transmission, and one was from a patient without evidence of neurological disease. There was no evidence of nAChR, but all tumors bound (‐)[³H]QNB in a saturable and specific manner. Dissociation constants derived from saturation isotherms ranged between 0.13 and 0.3 nM and maximum binding capacities between 35.4 and 181.7 fmol/mg protein (mean values for the five SCC). Competition studies revealed a pharmacological profile consistent with previous descriptions of mAChR. Competition by pirenzepine revealed only one class of binding sites, that with a relatively low affinity for pirenzepine. In the presence of the guanine nucleotide analogue 5′‐guanylyl imidodiphosphate, a decrease in affinity of the mAChR of SCC for oxotremorine was observed, with an increase in the pseudo‐Hill coefficient, but there was no change in the binding of atropine. The expression on SCC of mAChR, apparently of the M₂ subclass, represents yet another neural differentiation marker of SCC. It is noteworthy that the expression of this marker is not restricted to patients with an autoimmune paraneoplastic syndrome involving cholinergic neurons.