Desensitisation of muscarinic receptor-mediated cyclic GMP formation by cultured nerve cells

THE loss of sensitivity of a tissue to an agonist (perhaps a neurotransmitter) after prolonged exposure to this compound is called desensitisation and may be specific¹ or nonspecific². Although many different mechanisms may be involved in nonspecific desensitisation³, specific desensitisation (tachyphylaxis) has long been considered to involve the agonist-receptor complex^4-7. Our interest in the interaction of certain psychotropic drugs with muscarinic acetylcholine receptors of cultured nerve cells^8,9 has led us to study the desensitisation of these receptors. They mediate the formation of guanosine 3′,5′-cyclic phosphate (cyclic GMP)^8-10, a response which has yielded much information about the interactions of agonists and antagonists with the muscarinic receptor^8,9, although a direct coupling of this receptor and guanylate cyclase has not been demonstrated. We report here our use of this receptor effect to characterise the specific desensitisation of muscarinic acetylcholine receptors of intact mouse neuroblastoma cells (clone N1E-115).