Contribution of intra‐ and extracellular Ca²⁺ to noradrenaline exocytosis induced by ouabain and monensin from guinea‐pig vas deferens

Abstract

1 Contributions of intra-and extracellular Ca2" to noradrenaline (NA) release evoked by increasing intracellular Na+ concentrations (ouabain plus monensin) from adrenergic nerves of guinea-pig vas deferens were evaluated under conditions eliminating carrier-mediated NA release (with 100 gM cocaine).2 Ouabain (100 gM) plus monensin (10 gM), unlike 100 mM KC1, produced a marked NA release which was unchanged by Ca2"-removal. 3 In normal solution but not in Ca2"-free solution, the release of NA evoked by ouabain plus monensin was reduced by adenosine, clonidine and neuropeptide Y, and by Ca2+-channel blockers such as w-conotoxin GVIA and nifedipine. The release of NA was also decreased by cromakalim in a glibenclamide-sensitive fashion. 4 In contrast, in the absence but not in the presence of Ca2", the drug-evoked NA release was inhibited by mitochondrial inhibitors (carbonylcyanide-m-chlorophenylhydrazone and oligomycin) and further by immobilizers of intracellular Ca2`(TMB-8 and BAPTA-AM) and calmodulin antagonists (W-7 and trifluoperazine). 5These findings suggest that the release of NA evoked by elevation of [Na+]i from adrenergic nerves in the presence and absence of Ca2" involves, in part, exocytotic processes which are triggered by depolarization-induced Ca2`influx and by utilization of Ca2" from intracellular Ca2" store sites such as mitochondria, respectively.

Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens

“…A decrease in the [Na+],,/[Na+Ii ratio by reduction of [Na+I0 also results in tension development and the relative rate of contraction is inversely related to "a+], (Savineau et al, 1987;Sat0 and Aoki, 1991). In some smooth muscles, the responses evoked by high K+ solutions, ouabain, K+-free and low Na+ solutions are partially mediated by the release of neurotransmitters from nerve terminals (Tsuchiya et al, 1990;Katsuragi et al, 1994). The uterine smooth muscle receives both cholinergic and adrenergic innervation and is also innervated by SP-containing sensory nerves (Shew et al, 1991), indicating that uterine contractility may be influenced by neurogenic mechanisms.…”

“…It has been suggested that the increase in tension produced by an alteration in the Na+ gradient across the cell membrane may involve the following mechanisms: 1 ) Ca*+ intlux through voltagesensitive Ca2+ channels (VSCC) (Sato and Aoki, 1991;Katsuragi et al, 1994); 2) an increase in Ca2+ entry or decrease i n Ca2+ extrusion via the Na+/Ca2+ exchange mechanism (Savineau et al, 1987;Sato and Aoki, 1991); and 3) Ca2+ release from the sarcoplasmic reticulum (Lamb et al, 1988) or from the mitochondria (Katsuragi et al, 1994). The biphasic contractions induced by ouabain, K+free solution and low Na+ (25 mM) solution in rat uterus disappeared in a Ca2+-free medium, suggesting that these responses are strictly dependent on the presence of external calcium and do not involve Ca2+ release from intracellular stores.…”

Characterization of ouabain‐induced noradrenaline and acetylcholine release from in situ cardiac autonomic nerve endings

“…Most in vitro studies suggested that ouabain somehow increases intracellular Ca 2+ levels at the nerve endings and synaptosomes (Katsuragi et al. 1994, Casali et al.…”

“…1995, Wasserstrom & Aistrup 2005). Ouabain‐induced intracellular Na + accumulation could evoke an elevation of intracellular Ca 2+ level via Ca 2+ channel opening (Katsuragi et al. 1994), Ca 2+ release from internal stores (Nishio et al.…”