| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Research Abstract |
We have found that unlike catecholamine secretion induced by nicotinic receptor activation, the secretory response to muscarinic receptor stimulation is not simply resulting from increase in Ca^<2+> influx,but from mobilization of intracellulary stored Ca^<2+> in cat adrenal glands (Nakazato et al.,1984). Since the same was true in guinea-pig adrenal glands, Ca^<2+> stores linked to muscarinic receptor have been suggested to be present in the adrenal chromaffin cells, regardless of the species. In this research project, first, the possibility of the presence of Ca^<2+> stores other than those linked to muscarinic receptors was determined by using caffeine which has been known to initiate Ca^<2+>-induced Ca^<2+> release from sarcoplamic reticulum of the muscle. Secondly, the ability of subcellular organella to accumulate ^<45>Ca^<2+> was studied to specify the candidate for Ca^<2+> store, thirdly the effect of caffeine on Ca^<2+> mobilization or catecholamine secretion induced by acetyl
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choline and finally, the effect on membrane currents under the condition of whole cell patch clamp were investigated. The results are summarized in the following; (1) caffeine caused a marked increase in catecholamine secretion from adrenal chromaffin cells of cat, guinea-pig and ox, (2) the effectiveness of caffeine was depressed by the presence of extracellular Ca^<2+>, Mg^<2+> and/or Na^+, (3) ryanodine blocked the secretory response to caffeine, but partially inhibited the response to muscarinic stimulation. (4) Both endoplasmic reticulum and secretory granules had the capacity to accumulate ^<45>Ca^<2+> in a similar extent. (5) Caffeine inhibited catecholamine secretion induced by acetylcholine, high K^+ and veratridine. (6) Acetylcholine initiated nicotinic receptor current and depolarization evoked voltage-dependent Na^+, K^+ and Ca^<2+> in chromaffin cells and (7) all of these currents were inhibited by caffeine. These results suggest that the ineffectiveness of caffeine in releasing catecholamine in the presence of extracellular Ca^<2+> and/or Na^+ is due to the inhibitory action of caffeine itself on both receptor linked and volgate- dependent ionic channels. Less
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