G Protein-coupled Receptors

Signaling pathways can become really complex. The same signaling molecules can affect cells in different ways, depending on the environment inside the cell. Acetylcholine, for example, is a ligand that can have opposite effects in skeletal muscle and in heart muscle cells. It promotes muscle contraction in skeletal muscle and inhibits muscle contraction in heart muscle.

Many signaling pathways result in a cellular response because of a change in gene expression. Genes get expressed in order to make a protein. Regulation can occur at the transcription level or at the translation level.

Some of the signaling pathways will induce a metabolic response in the cell, increasing or decreasing the level of metabolic enzymes. Epinephrine is a hormone that does this through a cyclic AMP messenger. It causes the phosphorylation of two metabolic enzymes. Glycogen phosphorylase is activated, while glycogen synthase is inactivated. Glycogen gets broken down into glucose and no new glycogen gets made. The glycogen phosphorylase breaks down glycogen, while glycogen synthase makes glycogen.

G PROTEIN-COUPLED RECEPTORS

These have many names, most commonly, seven-pass transmembrane domain receptors, because they pass through the membrane seven times. They are a large family of receptors that activate certain signal transduction pathways, initiating cellular responses in the cell. They are only found in eukaryotic cells and involve odors, pheromones, neurotransmitters, light-sensitive compounds, and hormones. More than a third of medications are based on these receptors.

The two main pathways involved with these receptors are the cyclic AMP pathway and the phosphatidylinositol signal pathway. A ligand binds to the receptor and initiates a conformational change in the receptor. It activates a G protein by exchanging GDP attached to the protein for a GTP molecule.

No one knows the exact size of this superfamily but at least 810 different genes are involved in coding for them. There are six main classes of these receptors. Class A mainly deals with olfactory sensations. There are others that deal specifically with cyclic AMP and others that deal with pheromones. Some have no known function. Important

receptors of this category deal with taste, vision, smell, immune function, and mood regulation. Figure 53 is a depiction of the G protein-coupled receptor:

Figure 53.

The N-terminus of the receptor is on the outside and the C-terminus of the receptor is on the inside of the cell. When activated, a G-protein gets activated. What eventually happens depends on the G protein. GTP replaces GDP after the binding of the receptor takes place. Ligands can activate the protein, can inactivate the protein, or can have a neutral action on the protein. Activated G proteins contain GTP.