Catecholamine Secretion by the Adrenal Medulla
Chromaffin cells located in the adrenal medulla are responsible for producing catecholamines. The primary hormone stored in their secretory granules is epinephrine (adrenaline). Norepinephrine (noradrenaline) is synthesized in smaller amounts. Interestingly, ATP molecules and enkephalins are released into the bloodstream along with these hormones.
Under physiological resting conditions, secretion is low, and blood norepinephrine levels slightly exceed epinephrine concentration. The situation changes dramatically upon sympathetic nervous system activation: hormone release increases sharply. During short-term arousal, epinephrine dominates, but with prolonged stimulation, its proportion decreases, giving way to norepinephrine.
This process is controlled by the hypothalamus. Nerve impulses travel via sympathetic preganglionic fibers of the splanchnic nerve. Their terminals release the neurotransmitter acetylcholine, which binds to nicotinic cholinergic receptors, triggering catecholamine release into the blood. Inactivation of spent hormones involves monoamine oxidase (MAO) and catechol-$O$-methyltransferase (COMT), after which metabolites are excreted by the kidneys.
Adrenergic Receptors and Systemic Effects
The effects of catecholamines are mediated through specific G protein-coupled membrane receptors. They are divided into alpha and beta adrenergic receptors. Stimulation of $\alpha_1$ receptors leads to an increase in intracellular calcium concentration, whereas activation of $\alpha_2$ receptors decreases cAMP levels. Interaction with $\beta$ receptors, conversely, activates adenylate cyclase and increases intracellular cAMP.
Epinephrine has the highest affinity for $\beta$ receptors, and norepinephrine for $\alpha$ receptors. The number and sensitivity of these structures can change: they desensitize upon prolonged contact with agonists (desensitization via phosphorylation) and increase in sensitivity under the influence of glucocorticoids and thyroid hormones.
Main physiological effects of epinephrine:
- Metabolism: causes hyperglycemia (enhances glycogenolysis, activates gluconeogenesis, decreases glucose uptake by tissues), stimulates lipolysis, and increases basal metabolic rate.
- Cardiovascular system: via $\beta_1$ receptors, increases heart rate and contractility. In physiological doses, it dilates blood vessels in skeletal muscle and the liver, but constricts abdominal blood vessels. Notably, cutaneous blood vessels constrict at any concentration.
- Nervous system: stimulates the reticular formation, enhances attention, and decreases pain sensitivity (antinociceptive action).
Norepinephrine differs in that it causes generalized vasoconstriction, increasing both systolic and diastolic blood pressure (epinephrine raises only systolic). Furthermore, its effects on metabolism and the heart are less pronounced.
Endocrine Function of the Pancreas
The pancreatic islets (islets of Langerhans) synthesize key regulators of carbohydrate metabolism—insulin and glucagon. The main factor controlling their release is blood glucose level. Secretion is also modulated by the autonomic nervous system and the paracrine influence of somatostatin, which is produced in neighboring islet cells.
Insulin is a peptide hormone synthesized by $\beta$ cells. Its key task is to stimulate nutrient deposition and lower plasma glucose levels. By interacting with tyrosine kinase receptors, insulin activates glucose transporters in skeletal muscle, adipose tissue, and the myocardium.
Tissue effects of insulin:
- In the liver: inhibits gluconeogenesis and glycogenolysis while stimulating glycogen synthesis.
- In adipose tissue: blocks lipolysis and activates triglyceride formation from fatty acids (pronounced lipogenic effect).
- In muscles: promotes glycogen accumulation, enhances amino acid uptake, and stimulates protein synthesis, exerting a powerful anabolic effect.