In this chapter, we have focused primarily on signal transduction pathways activated by individual G protein–coupled receptors. However, even these relatively simple pathways presage the more complex situation within live cells. Many G protein–coupled receptors form homodimers or heterodimers with other G protein–coupled receptors that bind ligands with different specificities and affinities. Much current research is focused on determining the functions of these dimeric receptors in the body and the signal transduction pathways they trigger.

We have seen that rapid changes in the concentrations of free Ca²⁺ ions in the cytosol, ER, and mitochondria regulate several responses, including glycogen synthesis and catabolism, muscle contraction, and oxidative phosphorylation and ATP synthesis in mitochondria. Changes in mitochondrial Ca²⁺ levels also affect several other cell processes, including apoptosis (programmed cell death; see Chapter 21), mitophagy (degradation of nonfunctional mitochondria in lysosomes) and mitochondrial division and motility. Much remains to be learned about the regulation of these and many other cellular processes that depend on changes in Ca²⁺, including activation and inhibition of transcription factors and other gene-regulatory proteins.

As a result of signal transduction in many cells, Ca²⁺ levels increase in only part of the cytosol, such as near segments of the plasma membrane that are rich in Ca²⁺ channels, and not in the bulk of the cytosol. How these local concentrations of Ca²⁺ are maintained, and how the resultant Ca²⁺ gradients formed by diffusion affect cell function, are active and important current research questions.

Efforts to identify orphan GPCRs and other types of receptors continue to reveal novel hormones with important functions. As an example, a new neuropeptide, neuropeptide S, was identified as the ligand for a previously orphan GPCR. Researchers then showed that this neuropeptide modulates a number of biological functions, including anxiety, arousal, locomotion, and memory. One can only wonder what other peptides and small-molecule hormones remain to be discovered and the insights that study of these peptides will provide for our understanding of human metabolism, growth, and behavior.