Effects of veratridine on Ca fluxes and the release of oxytocin and vasopressin from the isolated rat neurohypophysis.

Abstract

A B S T R A C T Uptake of radioactive calcium, 4~Ca efflux, and hormone release from the isolated rat neurohypophysis were monitored in vitro after the addition of veratridine to the incubation medium. Veratridine dramatically increased hormone release, but the release rate was not sustained and had declined by about 90% after 2 h. Removal of external Na § prevented hormone release as did addition to the incubation medium of tetrodotoxin or the calcium antagonists D600 and Mn z+ ions. Veratridine increased 45Ca uptake into the isolated neurohypophysis and the increase could be prevented by addition of tetrodotoxin or D600 to the medium. Efflux of 4SCa was not changed by addition of veratridine. The results underline the importance of both Na + and Ca +2 channels in the regulation of secretion of neurosecretory products.

The effect of naloxone on vasopressin release from rat neurohypophysis incubated in vitro.

“…Vasopressin release in our system (at 9 Hz) was abolished in the presence of tetrodotoxin, the blocker of sodium channels (Narahashi, Moore & Scott, 1964), or in the absence of calcium ions from the superfusion medium. Thus, we feel justified to infer that the hormone release occurred following an action potential-induced, calcium-dependent secretary mechanism similar to that thought to occur in vivo (Nordmann & Dyball, 1978).…”

Inhibition by somatostatin of bovine growth hormone secretion following sodium channel activation.

“…An increase in sodium permeability in the presence of sodium would be expected to depolarize the plasma membrane and increase calcium entry through a potentialsensitive channel. Veratridine increases 45Ca incorporation into islets (Donatsch et al 1977) and posterior pituitary (Nordmann & Dyball, 1979) and to a lesser extent into anterior pituitary cells. Moreover, with the exception of Donatsch et al (1977), all the groups have reported that veratridine does not increase secretion in the absence of external calcium, and this is also the case for bovine growth hormone release.…”

“…It seems reasonable to conclude that the increase in 22Na content of bovine pituitary cells exposed to veratridine is due to the opening of a voltage-sensitive sodium channel. Veratridine has also been shown to stimulate release of insulin (Donatsch et al 1977;Pace, 1979), posterior pituitary 1c00 hormones (Nordmann & Dyball, 1979) and catecholamines (Ito et al 1979). In each case stimulation of secretion was prevented by tetrodotoxin and, when it was investigated, by sodium removal.…”

“…A similar spike of catecholamine release on re-introduction of calcium was observed by Ito et al (1979) for perifused guinea-pig adrenals after exposure to veratridine. The release of insulin (Pace, 1979) and posterior pituitary hormones (Nordmann & Dyball, 1979) by veratridine is also dependent on external calcium. The spike of growth hormone release in response to veratridine was completely prevented by verapamil (Fig.…”

“…Veratridine would therefore be expected to depolarize electrically active secretary cells, and this has been observed in islet cells (Pace, 1979). Veratridine also stimulates the release of insulin (Donatsch, Lowe, Richardson & Taylor, 1977;Pace, 1979), posterior pituitary hormones (Nordmann & Dyball, 1979) and catecholamines (Ito, Nakazato & Ohga, 1979), and this has been attributed to increased calcium entry following membrane depolarization. There is some evidence that the electrical activity of the anterior pituitary is modified by agents thought to be responsible for the physiological regulation of hormone release.…”