Husted S, Nedergaard O A
Acta Pharmacol Toxicol (Copenh). 1981 Nov;49(5):334-53. doi: 10.1111/j.1600-0773.1981.tb00916.x.
The effect of adenosine and adenine nucleotides on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta was studied. Adenosine (10(-5)-3 x 10(-4)M) decreased the contractile response of pulmonary artery and aorta evoked by electrical-field stimulation. The decrease was reversible. No tachyphylaxis developed. Inhibition of either adenosine deaminase by deoxycoformycin (3.6 x 10(-6)M) or of adenosine transport by dilazep (3 x 10(-6)M) did not alter the inhibitory effect of adenosine on the neurogenic contractions in the pulmonary artery. However, deoxycoformycin plus dilazep markedly enhanced the inhibitory effect of adenosine. The calcium antagonists nifedipine (1.5 x 10(-8)M) and nimodipine (1.3 x 10(-8)M) had no effect on the adenosine-induced inhibition. This was also the case with theophylline (5 x 10(-5)M), atropine (10(-7)M), and the prostaglandin synthetase inhibitors indomethacin (5 x 10(-5)M and suprofen (3 x 10(-5)M). The contractile response of the pulmonary artery elicited by exogenous (-)-noradrenaline (NA; 10(-9)-3 x 10(-4)M) was essentially not altered by adenosine (10(-5)-3 x 10(-4)M). Adenosine (10(-4)M) did not alter the spontaneous 3H-outflow from rabbit aorta preloaded with 3H-(-)-noradrenaline (3H-NA). Adenosine (10(-5)-3 x 10(-4)M), ADP (10(-4)M), ATP (10(-5)M), and inosine (10(-4)M) diminished the overflow of tritium from pulmonary artery and aorta preloaded with 3H-NA. The spontaneous outflow of tritium from aorta preloaded with 3H-NA consisted of 3H-NA (17%), 3H-dihydroxyphenylglycol (3H-DOPEG; 30%), 3H-dihydroxymandelic acid (3H-DOMA, 4%), 3H-O-methylated and deaminated metabolites (3H-OMDA; 42%), and 3H-normethanephrine (3H-NMN; 2%). Adenosine (10(-5) and 10(-4)M) enhanced 3H-DOPEG and 2H-NMN, decreased 3H-NA, and did not alter 3H-DOMA and 3H-OMDA. The stimulation-evoked overflow of tritium for aorta preloaded with 3H-NA consisted of 3H-NA (31%), 3H-DOPEG (18%), 3H-DOMA (2%), 3H-ONDA (46%), and 3H-NMN (3%). Adenosine (10(-5) and 10(-4)M) enhanced 3H-NA and 3H-DOPEG, decreased 3H-OMDA and did not alter 3H-DOMA and 3H-NMN. Adeosine (10(-6)-10(-4)M) did not alter the accumulation of 3H-NA (10(-8)M) by aorta. It is concluded that adenosine inhibits vascular sympathetic neuroeffector transmission by diminishing the release of transmitter from the nerve terminals.
研究了腺苷和腺嘌呤核苷酸对家兔离体肺动脉和主动脉交感神经效应器传递的影响。腺苷（10⁻⁵ - 3×10⁻⁴M）可降低电场刺激诱发的肺动脉和主动脉的收缩反应。这种降低是可逆的，未出现快速耐受性。脱氧助间型霉素（3.6×10⁻⁶M）抑制腺苷脱氨酶或双嘧达莫（3×10⁻⁶M）抑制腺苷转运，均未改变腺苷对肺动脉神经源性收缩的抑制作用。然而，脱氧助间型霉素加双嘧达莫可显著增强腺苷的抑制作用。钙拮抗剂硝苯地平（1.5×10⁻⁸M）和尼莫地平（1.3×10⁻⁸M）对腺苷诱导的抑制作用无影响。茶碱（5×10⁻⁵M）、阿托品（10⁻⁷M）以及前列腺素合成酶抑制剂吲哚美辛（5×10⁻⁵M）和舒洛芬（3×10⁻⁵M）也同样如此。外源性（-）-去甲肾上腺素（NA；10⁻⁹ - 3×10⁻⁴M）诱发的肺动脉收缩反应基本上不受腺苷（10⁻⁵ - 3×10⁻⁴M）影响。腺苷（10⁻⁴M）未改变预先用³H-（-）-去甲肾上腺素（³H-NA）标记的家兔主动脉的³H自发流出量。腺苷（10⁻⁵ - 3×10⁻⁴M）、二磷酸腺苷（ADP，10⁻⁴M）、三磷酸腺苷（ATP，10⁻⁵M）和肌苷（10⁻⁴M）可减少预先用³H-NA标记的肺动脉和主动脉的³H溢出量。预先用³H-NA标记的主动脉的³H自发流出物包括³H-NA（17%）、³H-二羟基苯乙二醇（³H-DOPEG，30%）、³H-二羟基扁桃酸（³H-DOMA，4%）、³H-O-甲基化和脱氨基代谢产物（³H-OMDA，42%）以及³H-去甲变肾上腺素（³H-NMN，2%）。腺苷（10⁻⁵和10⁻⁴M）可增加³H-DOPEG和³H-NMN，减少³H-NA，且不改变³H-DOMA和³H-OMDA。预先用³H-NA标记的主动脉的刺激诱发的³H溢出物包括³H-NA（31%）、³H-DOPEG（18%）、³H-DOMA（2%）、³H-ONDA（46%）和³H-NMN（3%）。腺苷（10⁻⁵和10⁻⁴M）可增加³H-NA和³H-DOPEG，减少³H-OMDA，且不改变³H-DOMA和³H-NMN。腺苷（10⁻⁶ - 10⁻⁴M）未改变主动脉对³H-NA（10⁻⁸M）的摄取。结论是，腺苷通过减少神经末梢递质的释放来抑制血管交感神经效应器传递。
