Summary
Highlights
Cells communicate to organize into tissues and organs, coordinate functions, and regulate development. This communication is mediated by 'mediators' (first messengers) that are captured by target cells.
Cell communication occurs through several modes: paracrine (neighboring cells), autocrine (self-signaling), nervous (neurotransmitters across synapses), and endocrine (hormones transported via blood to distant target cells).
In endocrine communication, mediators (hormones) are secreted into the blood to act on distant target cells. Examples include thyroid hormones regulating growth and metabolism, gastrointestinal hormones aiding digestion, leptin from adipose tissue, and hormones stored and released by the posterior pituitary (oxytocin, vasopressin).
Mediator solubility determines receptor location. Hydrophilic mediators (e.g., peptide hormones, catecholamines) bind to transmembrane receptors. Lipophilic mediators (e.g., steroid hormones) can cross the membrane and bind to cytoplasmic or nuclear receptors.
Hydrophilic messengers cannot enter cells directly. Upon binding to transmembrane receptors (often G-protein coupled receptors), they activate an enzyme (e.g., adenylate cyclase), leading to the production of intracellular second messengers like cyclic AMP (cAMP) and cyclic GMP (cGMP). cAMP activates protein kinase A, causing phosphorylation of various enzymes and biological responses, as seen with adrenaline's effect on heart rate.
Another G-protein-coupled system involves phospholipase C, which cleaves phosphatidylinositol diphosphate into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases calcium from the endoplasmic reticulum, while DAG activates protein kinase C, contributing to various cellular effects like vasodilation and the production of eicosanoids (e.g., prostaglandins).
Some peptide hormones like insulin and growth factors bind to transmembrane receptors with intrinsic enzymatic activity (tyrosine kinase). Upon ligand binding, these receptors autophosphorylate and phosphorylate intracellular signaling proteins, leading to diverse metabolic effects, such as glucose uptake into cells.
Lipophilic hormones (steroids, thyroid hormones, calcitriol) readily cross cell membranes. Steroid hormones bind to cytoplasmic receptors, forming a complex that translocates to the nucleus to regulate gene transcription. Thyroid hormones and calcitriol directly bind to nuclear receptors, influencing gene expression.
Nitric oxide (NO), a gaseous mediator produced by neurons and endothelial cells, acts locally. It diffuses rapidly into neighboring cells, activating soluble guanylate cyclase, which increases cGMP levels. cGMP then activates protein kinase G, leading to effects like vasodilation.