title: Facilitation of transmitter action on catecholamine output by cardiac glycoside in perfused adrenal gland of guinea-pig.
abstract: Effects of K+ deprivation and ouabain on catecholamine secretion evoked by splanchnic nerve stimulation (5 Hz), ACh (10(-5) M) and/or excess K+ (56 mM) were studied in isolated and perfused adrenal glands of guinea-pig. Exposure to K+-free Locke solution initially reduced and later enhanced catecholamine secretion sequentially evoked by splanchnic nerve stimulation and ACh. The enhancement attained a maximum, 185% in magnitude of the corresponding control response at 35 min for splanchnic nerve stimulation and 135% at 65 min for ACh after the start of exposure to K+-free solution. Ouabain (10(-5) M) caused a larger increase in the evoked catecholamine section than K+ deprivation did. The maximum effect was obtained from 40 to 50 min after the start of exposure to ouabain in which the magnitude of responses to splanchnic nerve stimulation, excess K+ and ACh was about 500, 400 and 300% of each control response, respectively. The effect of ouabain on the evoked catecholamine secretion increased as the concentration of extracellular Na+ was increased from 25 to 154 mM, regardless of the kind of stimuli. The ouabain-induced enhancement in the evoked responses was reversibly inhibited by removing Ca2+ from, or by adding Mg2+, Co2+ or Ni2+ to the perfusion medium. The ID50 values for Mg2+ were about 9.4 and 7.3 mM and those for Co2+ were 0.8 and 0.4 mM against ouabain on the responses to ACh and excess K+, respectively. The inhibitory effect of Mg2+ and Co2+ on the ouabain action was counteracted by increasing the concentration of Ca2+ from 2.2 to 8.8 mM in the perfusion medium. These results suggest that ouabain enhances catecholamine secretion evoked by splanchnic nerve stimulation, ACh and excess K+ by increasing the rate of Ca2+ influx through the ACh receptor linked Ca2+ channel and/or voltage-dependent Ca2+ channels on adrenal chromaffin cells of guinea-pig in a Na+-dependent manner.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism*; D006168:Guinea Pigs; D008274:Magnesium / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013153:Splanchnic Nerves / Q000502:physiology*
chemical_list: D003035:Cobalt; D010042:Ouabain; D012964:Sodium; D008274:Magnesium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D004837:Epinephrine