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DISCOVERING THE BRAIN
dilation in those of muscle. As another example, ACh's effect of constricting skeletal muscle cells can be blocked by curare but not by atropine, although the two alkaloids are in some ways similar; in smooth muscles of the intestine, however, the action of ACh can be blocked by atropine but is unaffected by curare. Clearly, the receptor molecules in the two locations have somewhat different shapes, despite their both being devised to respond to ACh.
Acetylcholine also serves to illustrate another level of complexity in the brain's signaling system. In muscle cells, it acts directly, moving positively charged sodium ions into the cell and depolarizing it. In the brain, however, this transmitter works in tandem with a “second messenger,” which conveys the signal inside the cell, sometimes amplifying it greatly in the process. (In this sense, the neurotransmitter that traverses the synapse is the “first messenger,” although this term is rarely used.)
To date, researchers have identified only two second-messenger systems —which is perhaps just as well for those who wish to understand neurophysiology, because the other kinds of messenger systems identified in the brain are proliferating so rapidly. One system uses the small molecule cyclic adenosine monophosphate (cyclic AMP) as its second messenger; the other system uses the even smaller calcium ion (Ca2+) and two compounds made up partly from the cell membrane itself: inositol triphosphate (IP3) and diacylglycerol (DG).
Both second-messenger systems have the same goal: to bring about a change in the shape of proteins inside the cell, which either enables or halts such activities as contraction (in a muscle cell, for example) or secretion (in a glandular cell). And both second-messenger systems begin in the same way: the receptor site at the cell membrane surface activates one of the so-called G-proteins (which require guanosine triphosphate to carry out their function). The G-protein in turn activates an enzyme within the membrane, causing a chemical reaction that assembles the second-messenger molecules from precursor molecules available inside the cell. Here the two systems diverge: in one, the enzyme adenylate cyclase removes two phosphate groups from adenosine triphosphate (incidentally releasing energy to the cell) and converts it into cyclic AMP. In the other