Peripheral catecholamine release by ?-latrotoxin in the rat

Abstract

Intraarterial injection of alpha-latrotoxin (alpha LTx), the major toxin of the black widow spider (Latrodectus mactans tredecimguttatus) venom, into carotid catheterized rats, induced prompt and marked rises in plasma adrenaline and noradrenaline concentrations, indicating that the toxin stimulates catecholamine release from both the adrenal medulla and sympathetic nerve terminals. Pretreatment with the ganglionic blocker chlorisondamine greatly reduced the plasma adrenaline response to alpha LTx but had almost no effect on the noradrenaline response, indicating that alpha LTx-stimulation of sympathetic nerve terminals is direct, whereas catecholamine release from the adrenal medulla is probably mediated by preganglionic release of acetylcholine. In vitro, alpha LTx induced a dose-dependent release of 3H-noradrenaline from rat irides preincubated with this radioactive amine and this effect was not changed by chlorisondamine plus atropine. By contrast, the toxin had no effect on 3H-noradrenaline release from suspensions of cultured rat chromaffin cells. Specific, high affinity binding of 125I-alpha LTx in iris and adrenal medulla homogenates was found to be exceedingly low, suggesting that it might be restricted to nerve terminals. No 125I-alpha LTx binding was seen nor could any effect of the toxin on 14C-5-hydroxytryptamine release be found in rat blood platelet preparations. alpha LTx binding and its amine releasing effect seem, therefore, to be specific for neurons and absent from other cells, even those, like adrenomedullary cells and blood platelets, which share with neurons their origin and/or other important characteristics.

Penelope’s web: using α‐latrotoxin to untangle the mysteries of exocytosis

“…The toxin has also been shown to stimulate exocytosis form non‐neuronal excitable cells, such as PC12 cells (Grasso et al. 1982), chromaffin cells (Picotti et al. 1982), pancreatic β‐cells and cell lines (Lang et al.…”

“…Endocrine cells, containing large dense‐cored granules, are also insensitive to α‐LTX in the absence of Ca 2+ (Grasso et al. 1982; Picotti et al. 1982).…”

α-Latrotoxin and Its Receptors

“…The effects of α-LTX on neurosecretion were first described on a cellular level in the 1970’s at frog neuromuscular junctions (NMJ) (Longenecker et al 1970; Frontali et al 1976), and later in mouse brain slices (Tzeng et al 1978), in synaptosomes (isolated brain nerve terminals) from rat (Grasso et al 1978), dog (Tzeng and Siekevitz 1979) and guinea pig (Nicholls et al 1982), primary cerebellar granule cell cultures (Grasso and Mercanti-Ciotti 1993) and in hippocampal organotypic cultures (Capogna et al 1996). In addition, catecholamine-secreting chromaffin cells (Picotti et al 1982) and PC12 cell line (Robello et al 1987), insulin-secreting pancreatic β-cells in primary or derived cell cultures (Lang et al 1998), oxytocin- and vasopressin-secreting neurohypophysis cells (Hlubek et al 2003) and luteinising hormone-secreting rat gonadotropes (Tse and Tse 1999) were also used to characterise the toxin’s effects on secretion from non-neuronal excitable cells. A secretory cell not sensitive to α-LTX still remains to be found.…”

Single-cell measurements of quantal secretion induced by α-latrotoxin from rat adrenal chromaffin cells: dependence on extracellular Ca2+

“…However, conflicting data exist in the literature concerning the ability of a-LT to induce release of catecholamines from dense core vesicles in adrenal chromaffin cells. Intravenously injected venom appears to have little effect on catecholamine release from adrenal chromaffin cells in situ [24]. In contrast, chromaffin cells cultured for days in the presence of nerve growth factor develop responsiveness to a-LT as a secretogogue [131.…”