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Adrenaline, also called epinephrine, is an endogenous catecholamine messenger: the body makes it and can release it into blood as a hormone. The adrenal medulla, the inner region of an adrenal gland, secretes adrenaline in response to sympathetic nervous system stimulation. A circulating hormone broadcasts a signal, but each receiving biological cell interprets it through its own receptors and intracellular machinery. Adrenaline activates both alpha-adrenergic receptors and beta-adrenergic receptors; it does not command one identical response everywhere.^[ref][ref]

Fuel mobilization is a useful example. A beta-adrenergic receptor can increase adenylyl cyclase activity through a stimulatory G protein, increasing the intracellular second messenger cAMP. Protein kinase A responds to cAMP; a phosphorylation relay through phosphorylase kinase activates glycogen phosphorylase, favoring glycogenolysis. Here adrenaline is the extracellular message, cAMP is the intracellular message, and glycogen is the reserve being mobilized. These are three different roles.^{[ref][ref][ref]}

The two reserves provide different material. Glycogenolysis draws on glycogen; lipolysis breaks down stored triglycerides, releasing fatty acids and glycerol. A skeletal muscle biological cell's own reserve and fuel released by adipose tissue are different supplies. Increasing a signal cannot mobilize an empty reserve: receptor activation changes the use of available material rather than creating fuel. The adrenergic adipocyte assay below gives direct human evidence for the lipolysis branch.^[ref]

Receptor context can even oppose this branch. In the human adipocyte preparation below, beta-adrenergic receptors promoted cAMP accumulation, whereas alpha-2 adrenergic receptors opposed it. Alpha-1 adrenergic receptors were associated with a different phospholipid readout. The balance of these responses matters more than the name of the messenger alone.^[ref]

This separation is useful when explaining signal transduction: ask which receptor is present, which relay it controls, which reserve or target is available, and which response was actually measured. Receptor binding occupancy, second messenger production and final fuel release are distinct observations. A stronger cAMP signal need not imply an equally large change in every downstream process; substrate availability and the rest of the receiving biological cell still matter.

The extract-transfer experiment under second messenger supplies the earlier experimental separation between hormone reception and an intracellular intermediary. Its existing account includes the preparations and controls. The complementary adrenergic adipocyte assay asks a different question: can the same adrenaline stimulus engage opposing receptors within a human preparation?

Glucagon is a peptide hormone made by alpha cells in the pancreatic islets. Its mature polypeptide has 29 amino acid residues. Alpha cells store glucagon in secretory granules and release it by exocytosis. Glucagon is a message about fuel availability; glucose is the sugar whose supply it helps regulate. A falling blood glucose concentration favors glucagon release, whereas a rise usually suppresses it. Amino acids can also stimulate release, so a meal containing protein need not produce the same hormone pattern as a meal dominated by carbohydrates. ^[ref]

The principal blood glucose-raising target is the liver. In a hepatocyte, the glucagon receptor is a G protein-coupled receptor: activation of a stimulatory G protein drives adenylyl cyclase, increasing the second messenger cAMP and activating protein kinase A. Downstream phosphorylation, including the phosphorylase kinase relay to glycogen phosphorylase, favors glycogenolysis. Glucagon also supports gluconeogenesis. These are different supplies: glycogenolysis draws on a finite glycogen reserve, whereas gluconeogenesis makes glucose from other substrates and depends on their availability. Longer fasting depletes the glycogen reserve; a stronger hormone signal cannot release material that is no longer there. ^{[ref] [ref]}

Do not copy the liver pathway into every target of insulin. Skeletal muscle uses its own glycogen reserve locally; its glucose uptake and the liver's glucose output are different flows. Nor is direct glucagon-stimulated lipolysis in human adipose tissue as firmly established as its action in the liver. Glucagon action depends on the tissue, other hormones, and available substrates. ^[ref]

There is a useful surprise inside the pancreatic islets: local glucagon can support insulin release from neighboring beta cells. The islet perifusion experiment distinguishes that interaction from glucagon's action on the liver. Thus the two hormones can oppose each other's effects on blood glucose while cooperating locally. Delta cells supply another local brake through somatostatin. ^{[ref] [ref]}