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 complex4-7. Our interest in the interaction of certain psychotropic drugs with muscarinic acetylcholine receptors of cultured nerve cells8,9 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 receptor8,9, 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).
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