Cytoplasmic concentrations

It is possible to deplete the brain of both DA and NA by inhibiting tyrosine hydroxylase but while NA may be reduced independently by inhibiting dopamine jS-hydroxylase, the enzyme that converts DA to NA, there is no way of specifically losing DA other than by destruction of its neurons (see below). In contrast, it is easier to augment DA than NA by giving the precursor dopa because of its rapid conversion to DA and the limit imposed on its further synthesis to NA by the restriction of dopamine S-hydroxylase to the vesicles of NA terminals. The activity of the rate-limiting enzyme tyrosine hydroxylase is controlled by the cytoplasmic concentration of DA (normal end-product inhibition), presynaptic dopamine autoreceptors (in addition to their effect on release) and impulse flow, which appears to increase the affinity of tyrosine hydroxylase for its tetrahydropteridine co-factor (see below). 

Ca2+ is an important second messenger in cells of the immune system, including T lymphocytes (Feske 2007). Normally, its cytoplasmic concentration is maintained within a narrow range (e.g., <0.1 pM) by a variety of pumps that serve to sequester Ca2+ in intracellular stores such as the... 

Glucose 6-phosphate is metabolized by both the glycolytic pathway (Chapter 16) and the pentose phosphate pathway. How is the processing of this important metabolite partitioned between these two metabolic routes The cytoplasmic concentration of NADP+ plays a key role in determining the fate of glucose 6-phosphate. 

Experiments in DAT-KO mice (37) clearly illustrated that although the interaction of amphetamine with the DAT is pivotal in its action, an involvement of other critical processes is important as well. Particularly, the role of vesicular storage of DA in amphetamine action has been highlighted in these mice (37). For example, while amphetamine-induced elevation of striatal DA did not occur in mice lacking DAT, the vesicle-depleting action of amphetamine was still observed (37). Furthermore, it has been suggested that amphetamine-triggered reverse transport of DA from cytoplasm to extracellular space does not occur simply due to an elevated cytoplasmic concentration of DA but requires direct action of amphetamine on the DAT (37). 

Methamphetamine evokes an initial increase in the cytoplasmic concentrations of free or unbound DA and 5-HT prior to their massive release ... 

T7ie price o f extrusion. What is the free-energy cost of pumping Ca out of a cell when the cytoplasmic concentration is 0.4 the extracellular concentration is 1.5 mM, and the membrane potential is —60 mV ... 

Under normal conditions, the extraceUnlar concentration of calcium is in the milhmolar range (l(h M), whereas its intracellular concentration is less than l(h M. The cytoplasmic concentration of calcium is increased through the actions of receptor-operated channels, voltage-activated channels, or ionic pumps. In addition, calcium can be released from internal stores (see also Figure 103). 

---