Effects of veratridine, tetrodotoxin and other drugs that alter electrical behaviour on secretion of melanocyte-stimulating hormone from melanotrophs of the pituitary pars intermedia

Since melanotrophs are electrically active and exhibit spontaneous Na spikes, a study was made of the effects, on melanotroph secretion, of drugs known to influence electrical properties. The output of melanocyte-stimulating hormone was measured from perifused neurointermediate lobes of mice or melanotrophs dispersed from such lobes of mice or rats. Veratridine (200 microM), which is known to increase Na permeability in a variety of cells, caused a large, although transient, increase in secretion from the melanotrophs that required extracellular Ca2+ and was blocked by the Na-channel blocker tetrodotoxin (1 microM). Tetraethylammonium (10 mM), which blocks K channels and thus prolongs the duration of the action potential in many cells, also stimulated secretion in the melanotrophs in a Ca-dependent manner. This response was not, however, blocked by tetrodotoxin, and is thus not attributable to prolongation of Na spikes in these cells. Moreover, tetrodotoxin did not inhibit basal secretion. The stimulant effect of veratridine on secretion in melanotrophs and its suppression by tetrodotoxin suggests that voltage-dependent Na channels can participate in the regulation of hormone output in these cells of the pituitary pars intermedia. However, the apparent lack of effect of tetrodotoxin on basal secretion suggests that the spontaneous Na spikes previously observed in these cells are not required for promoting the Ca influx which other evidence shows is important for basal secretion.