Identifying links in the chain: the dynamic coupling of catecholamines, peptide synthesis, and peptide release in...

Compared to neurons that communicate using synapses, some neuroendocrine neurons release relatively large quantities of peptide into the vasculature to control neuroendocrine function. Maintaining adequate amounts of peptide for release through controlled biosynthesis is therefore critical for their function. But how neuroendocrine-or in fact, any neuropeptide-neurons link appropriate levels of peptide biosynthesis with the action potentials that drive peptide release is unknown. Here, we review possible mechanisms in paraventricular hypothalamic CRH neuroendocrine neurons to coordinate these processes in response to catecholaminergic inputs. We show that CRH synthesis and release mechanisms are not invariably linked as CRH neurons are activated. Instead, coupling mechanisms exist in the premotor network that provides their synaptic inputs and in their intracellular signal transduction mechanisms, where transmitter-regulated phosphorylation of p44/42 mitogen-activated protein kinases (ERK1/2) may play a prominent role. These versatile and dynamic coupling mechanisms provide a way to link peptide biosynthesis and release.