Friday, 18 January 2019

cell biology - If so many different hormones/molecules work by activating adenylyl cyclase, how do they have different effects?


It seems that many hormones and molecules work by activating adenylyl cyclase to convert $\text{ATP}$ to $\text{cAMP}$, such as adrenaline and glucagon. Both of these seem to bind to $\text G$ protein receptors, cause an alpha subunit to dissociate and bind to adenyly cyclase to activate it, and then adenylyl cyclase forms $\text{cAMP}$. If so many molecules work in the same way, how can they have different effects?


My guess is that perhaps they may have different molecules inside which respond differently to elevated levels of $\text{cAMP}$? I presume both cells affected by adrenaline and by glucagon have the protein kinase which, when activated by $\text{cAMP}$, is able to activate glycogen phosphorylase to break down glycogen, as both adrenaline and glucagon increase blood sugar levels. Perhaps liver cells have more of the glycogen phosphorylase enzyme for a greater rate of breakdown of glycogen?


But then when I consider the heart, adrenaline increases heart rate but glucagon does not. If they have the same mechanism of action, how can this discrepancy arise? Could it perhaps be that adrenaline increases heart rate not by acting in the heart cells but in the medulla oblongata to increase the heart rate? But then again I come to the problem of why glucagon does not have the same effect. In this case I could hazard a guess that the glucagon molecule is too large to pass across the blood brain barrier.


But this is just one example of a possible problem in how two different molecules use the same mechanism. Although I cannot find a link now, I think I remember that long term potential ion to for new memories involves activation of adenyl cyclase. If that is so, it doesnt make much sense becaus adrenaline certainly doesn't help in the formation of new memories!


EDIT: I have just also read that insulin works by activating cAMP in hepatocytes/muscle cells, however it also seems that glucagon works by activating cAMP in the same cells! Two directly opposing effects using the same mechanism in the same cells- I'm very confused now!




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