A medical research center is studying therapeutic options for the treatment of neuromuscular disorders. During experimentation, scientists develop a new drug that seems to have partial agonist/antagonist activity against receptor X. When the experimental drug is applied to cells expressing receptor X, there is an immediate change in transmembrane calcium, sodium, and potassium flow secondary to the opening of the receptor channel. Receptor X is most likely which type of receptor?

Question

A medical research center is studying therapeutic options for the treatment of neuromuscular disorders.  During experimentation, scientists develop a new drug that seems to have partial agonist/antagonist activity against receptor X.  When the experimental drug is applied to cells expressing receptor X, there is an immediate change in transmembrane calcium, sodium, and potassium flow secondary to the opening of the receptor channel.  Receptor X is most likely which type of receptor?

Quizplus · Accepted Answer

Cell membrane receptors can be divided into two broad categories: ionotropic receptors (ion channels that open directly upon ligand binding) and metabotropic receptors (these receptors utilize second messengers to indirectly influence their corresponding ion channels). Nicotinic cholinergic receptors of the neuromuscular junction are an example of a ligand-gated ion channel receptor (ionotropic receptor). As an action potential progresses to the presynaptic terminal, voltage-gated calcium channels open and allow entry of calcium into the nerve cytoplasm. This triggers the fusion of storage vesicles with the membrane, allowing a release of acetylcholine (ACh). This ACh diffuses across the synaptic cleft and ultimately interacts with nicotinic cholinergic receptors present on the motor end-plate. These receptors are ion channels that are comprised of five subunits with two ACh binding sites. If, and only if, both binding sites are filled, the ion channel will open. There is subsequent sodium and calcium influx and potassium outflux that results in the generation of an end-plate potential. Nicotinic cholinergic receptors are also found in the CNS and on postganglionic neurons of autonomic ganglia. The description in the question stem most likely represents a nicotinic cholinergic receptor given the immediate flux of sodium, calcium, and potassium demonstrated by the scientists. (Choice A) Binding of epinephrine to α1 adrenoceptors results in the activation of the inositol triphosphate (IP₃) pathway. This pathway results in increased intracellular calcium via release of Ca²⁺ from storage organelles. (Choices B & C) β1 and β2 adrenoceptors are associated with the cAMP signal transduction pathway. Stimulation of these receptors causes protein kinase A activation. (Choice D) M1 and M3 muscarinic receptors utilize the inositol triphosphate pathway to increase intracellular calcium concentration and activate protein kinase C. M2 muscarinic receptors act via the cAMP second messenger system, and when activated decrease intracellular cAMP concentrations. Educational objective: The autonomic nervous system utilizes three types of signal pathways: cAMP, IP₃, and ion channels. Nicotinic receptors are ligand-gated ion channels that open after binding acetylcholine. This results in an immediate influx of Na⁺ and Ca²⁺ into the cell and an outflux of K⁺ from the cell. __________ References: Neuromuscular junction in health and disease. (http://www.ncbi.nlm.nih.gov/pubmed/17573397)

A Medical Research Center Is Studying Therapeutic Options for the Treatment