Calmodulin in neurotransmitter and hormone action.

Although CaM exists in abundance in many cells, it can be regulated by hormones and neurotransmitters on several levels in a variety of tissues and systems. Neurotransmitter action can lead to a rapid and direct activation of CaM-dependent enzymes or binding of CaM to other CaM-BPs, while persistent stimulation results in a redistribution of CaM and CaM-BPs on a slightly longer time-scale. Long-term neurotransmitter or hormone action or changes in their activity due to drug intervention may lead to changes in cellular CaM content. Both the change in localization of CaM and the long-term increases in CaM content will result in an increase in the sensitivity of Ca(2+)-related processes in select areas. The change in CaM content may be a homeostatic response that would signal an enhanced requirement and sensitivity for a Ca2+/CaM-dependent process or a compensatory reaction titrating chronic changes in Ca2+ within the cell. Both CaM content and localization are highly responsive to changes in [Ca2+]i, but other messengers such as cAMP play a distinct role in both processes. Many changes in CaM, both short and long-term, may involve rearrangements of cytoskeletal proteins, since many CaM-BPs have cytoskeletal localizations and binding of CaM to many of the proteins affects cytoskeletal protein-protein interactions. Therefore, changes in CaM distribution and content, besides altering the activities of the many CaM-dependent enzymes, could also be involved in restructuring in cytoskeletal processes, such as synaptic morphology, vesicular or protein transport, or secretion, that result from an initial neurotransmitter or hormone stimulation.