The Effect of Veratridine on the Release of Catecholamines From the Perfused Adrenal Gland

Abstract

Experiments on perfused adrenal glands of guinea‐pigs were carried out to study the catecholamine output induced by veratridine in the presence of hexamethonium and atropine. Veratridine (10 μm to 200 μm) caused a dose‐dependent increase in catecholamine output. The addition of veratridine to the perfusion medium for a period of 3 min caused an increase in catecholamine output which reached a maximum 5 min to 10 min after withdrawal of the drug. The catecholamine output then gradually declined and reached near resting values within 30 minutes. It was never sustained for a longer period, even when veratridine was infused for 1 hour. Veratridine failed to increase the catecholamine output in the absence of extracellular Ca2+. However, the addition of Ca2+ after an infusion of veratridine (100 μm) in the absence of Ca2+ caused an increase in the catecholamine output which was proportional to the concentration of Ca2+ (0.55 mm to 8.8 him) used. Veratridine did not increase the catecholamine output in the absence of extracellular Na+ ions, NaCl being replaced by equimolar choline chloride or LiCl. Veratridine also failed to evoke catecholamine output in a Na+‐ffee solution in which Na+ was replaced by sucrose; this was the case even in the presence of a high concentration of Ca2+ (8.8 mm). Tetrodotoxin (0.1 μm) and excess Mg2+ (20 mm) reversibly inhibited the catecholamine output induced by veratridine. Ouabain (10 μm) significantly potentiated the veratridine‐induced catecholamine output. It is suggested that Na+‐dependent Ca2+ influx as well as voltage‐dependent Ca2+ influx mechanisms may be involved in the catecholamine output induced by veratridine.

Inhibitory effects of caffeine on secretagogue‐induced catecholamine secretion from adrenal chromaffin cells of the guinea‐pig

“…Table 2). In agreement with previous results (Teraoka et al, 1991) (20 mM (Douglas & Rubin, 1961;Ito et al, 1978;1979;Kilpatrick et al, 1981;Knight & Baker, 1983;Knight & Kesteven, 1983;Wakade & Wakade, 1983). However, the mechanism underlying the depolarization is different between stimulants, ACh and veratridine cause depolarization resulting mainly from the activation of nicotinic receptor channels and voltage-dependent, tetrodotoxin-sensitive Na' channels, respectively.…”

“…Both adrenal glands were perfused and isolated following the general procedure described previously (Ito et al, 1979). The glands were perfused at a flow rate of 0.5 to 0.6 ml min'-and maintained at room temperature (approximately 25C).…”

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

“…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.…”

“…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.…”

Release of 5‐hydroxytryptamine, dopamine and noradrenaline in the rat vas deferens in the presence of compound 48/80, veratridine or K+

“…Therefore, it is possible that the content of dopamine in both kinds of vesicles is different. The difference between vereatridine and K+ with respect to the fractional release of dopamine and NA in the rat vas deferens could be a consequence of the distinct ionic movements across the cell membrane, caused by either depolarizing agent (Ito et al, 1979;AdlerGraschinsky et al, 1984). The preferential release of dopamine over NA, induced by veratridine (this study) resembles the overflow of these amines during transmural nerve stimulation of the rat and guineapig vas deferens (Bell et al, 1984).…”