An Introduction to Mechanisms in Pharmacology and by Howard Rogers and Roy G. Spector (Auth.)

By Howard Rogers and Roy G. Spector (Auth.)

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Conversely the fact that the 5-HT receptor is heat stable would fit better with the suggestion that it is a protein rather than a ganglioside. The actual isolation of receptor molecules is of an even greater order of difficulty. Basically two approaches have been adopted. One involves the separation of the membrane into its various components and then assaying these components for the binding of agonists and antagonists appropriate to the receptor under consideration. The other depends upon the use of agents which bind covalently to the receptor the tissue then being fractionated and the receptor isolated by virtue of its attachment to the marker agent.

44 MECHANISMS IN PHARMACOLOGY A N D THERAPEUTICS The chemical reaction by which ATP makes energy available for active + + ++ sodium pumping is catalysed by an enzyme, Na —, K —, M g stimulated + + ++ adenosine triphosphatase ( N a - , K - , M g ATPase). The reaction catalysed is summarised as ATP -> ADP + P f + utilisable energy. The enzyme is a membrane protein and is inhibited by cardiac glycosides such as ouabain or digoxin. These drugs have to be applied to the outer face of the cell membrane and are ineffective if injected inside the cell.

In summary, three sources of "coupling" calcium are distinguished: bound intracellular calcium; free intracellular calcium and extracellular ions bound to the cell membrane. Present techniques do not allow a clear distinction to be made between these sources. It has not been established that the membrane coupling process is identical in other types of muscle. In cardiac muscle there is a greater dependence on the extracellular calcium ion concentration than in skeletal muscle but even so, the major source of calcium ion mobilised during contraction is intracellular.

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