Intracellular messengers

Second messenger concept

Small intracellular messengers link extracellular signals to intracellular responses.

Adenylyl cyclase

Converts ATP to cAMP; different isoforms integrate signals using allosteric regulation.

Role of αs-GTP

Activates adenylyl cyclase to stimulate cAMP production.

Phosphodiesterases (PDEs)

Degrade cAMP; targets of drugs like caffeine and theophylline.

PKA structure

Tetramer of 2 regulatory and 2 catalytic subunits; cAMP binding releases active catalytic subunits.

AKAP scaffolding

Localise PKA and associated signalling proteins to specific sites.

cGMP similarities to cAMP

Made by guanylyl cyclase, degraded by phosphodiesterases, and activates protein kinase G.

PDE5 inhibition

Mechanism of Viagra; increases cGMP in smooth muscle, promoting vasodilation.

PLC signalling pathway

Cleaves PIP2 into DAG (activates PKC) and IP3 (releases Ca²⁺ from endoplasmic reticulum).

DAG properties

Lipid-anchored, activates PKC; phorbol esters mimic it but cannot be degraded.

IP3 actions

Diffuses to endoplasmic reticulum and triggers Ca²⁺ release through IP3 receptors.

PIP2 as regulator

Decrease in PIP2 also modulates ion channels after PLC activation.

Termination of PLC signals

DAG phosphorylation and IP3 dephosphorylation; IP1→inositol step blocked by lithium.

Calmodulin role

Ubiquitous Ca²⁺ sensor regulating many intracellular targets.

Ca²⁺ spikes

Frequency-encoded signals that allow digital-like intracellular communication.

Spatial specificity of Ca²⁺ signals

Localised Ca²⁺ release enables distinct responses in different subcellular regions.