Second messengers carry the secretory stimulus from the nerves into the secretory cells and provide a flexible coupling between the intracellular and extracellular environments
The link between 1st (neurotransmitter) and 2nd mesenger is a plasma membrane receptor for the neurotransmitter. Even though fluid and protein secretion are under the control of different neurotransmitters (ACh & NorAd, respectively) the receptors on salivary acinar cells for neurotransmitters belong to the same 7-membrane spanning domain family of receptors. The coupling of ACh to Ca2+ and that of NorAd to cAMP share the same general outline. In both, the second step in stimulus-secretion coupling is binding of neurotransmitter to receptor and activation of a G-protein coupled intracellular enzyme
Members of the 7-membrane spanning domain superfamily of receptors are linked to heterotrimeric G-proteins. On activation by neurotransmitter (1), the G-protein binds GTP instead of GDP and the thus activated α subunit dissociates from the βγ subunits (2). The α subunit binds to and activates a target enzyme (3).
This process has built in amplification because the target enzyme is stimulated to generate molecules of 2nd messenger for as long as the α subunit of the G-protein has GTP bound to it. In fact, the process only switches off at all because the α subunit has a intrinsic GTPase activity which (slowly) hydrolyses GTP to GDP. An α subunit with GDP bound to it cannot activate the target enzyme and so the process stops. Amplification is one of the most significant aspects of 2nd messenger signalling because it transduces a very small extracellular stimulus is into a large intracellular event.
Fluid and electrolyte secretion is activated by binding of ACh to muscarinic M3 ACh receptors. The G-protein is called Gq and the target enzyme is phospholipase C (PLC) which splits phosphatidyl 4,5, bisphosphate (PIP2) into diacylglycerol (DAG) and Inositol 1,4,5 trisphosphate (IP3)
Macromolecule (protein) secretion is activated by binding of NorAdrenaline to β adrenergic receptors. The G-protein is called Gs and the target enzyme is adenylate cyclase which converts ATP into cAMP.