Optimizing release from peptide hormone secretory nerve terminals

Abstract

Secretion of the peptide neurohormones oxytocin and vasopressin from terminals of magnocellular neurones in the mammalian neurohypophysis is elicited by conduction of depolarizing action potentials into terminal membranes, inducing opening of voltage-sensitive Ca2+ channels, entry of Ca2+ from the extracellular space and a rise in cytoplasmic Ca2+ concentration. The amount of peptide released per action potential is not immutable. In particular, the patterns in which action potentials are generated at the cell somata of the two types of neurone each appear exquisitely suited to optimize the release process at the terminal by utilizing a frequency-facilitation mechanism and by minimizing a mechanism of fatigue in the release process. The different properties of oxytocin and vasopressin neurones are of important physiological significance. The secretory terminals are also a site of receptor-mediated influences of neuromodulators which can greatly alter release efficiency. The mechanisms underlying facilitation and fatigue are not clearly understood. The evidence suggests that processes both prior to depolarization of the terminals (propagation and form of the action potentials) and directly at the terminals (frequency/pattern-dependent Ca2+ entry and channel openings) are involved. Transient activity-related increases in extracellular K+ concentration may be involved at both sites. Two types of neuromodulation have been partly characterized. Kappa-Opioid receptors in secretory terminal membranes directly modulate depolarization-evoked peptide release probably via interactions with Ca2+ channels. beta-Adrenergic receptors localized on neurohypophyseal astroglial cells mediate more subtle effects of noradrenaline. In the more chronic situation the neurohypophyseal astroglia alter their morphological relationships with neurosecretory elements and the basal lamina at release sites, changes which may also serve to optimize the secretory process.