Long-term regulation of muscarinic acetylcholine receptors on cultured nerve cells

John E. Taylor, Esam El-Fakahany, Elliott Richelson

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75 Scopus citations


Incubation of mouse neuroblastoma cells (clone 1LE-115) with the muscarinic agonist, carbachol, resulted in a time-dependent desensitization to muscarinic receptor-mediated cyclic GMP formation and a decrease in the number and affinity of muscarinic receptors as measured by the binding to intact cells of the muscarinic antagonist, [3H]quinuclidinyl benzilate (QNB). The decrease in responsiveness to cyclic GMP formation reached a maximum after a 15-minute exposure to 1 mM carbachol (short-term desensitization) whereas changes in [3H] QNB binding became apparent only after a one hour exposure and reached a maximum after about 12 hrs (long-term desensitization). Recovery of sensitivity after short-term desensitization was rapid, suggesting that this process may involve a conformational change in the muscarinic receptor. In contrast, recovery after long-term desensitization was prolonged and could be slowed by the inhibition of protein synthesis. These results indicate that different cellular mechanisms are involved in the short-term and long-term desensitization of muscarinic receptors.

Original languageEnglish (US)
Pages (from-to)2181-2187
Number of pages7
JournalLife Sciences
Issue number26
StatePublished - Dec 24 1979

Bibliographical note

Funding Information:
This work was supported by the Mayo Foundation and USPHS Grants (MH 27692, MH 07925 and DA 1490) .


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