Ishii-Nozawa R, Shinozuka K, Kunitomo M, Takeuchi K, Hashimoto T
Meiji Pharmaceutical University, Kiyose, Japan.
Yakugaku Zasshi. 1999 Jun;119(6):417-28. doi: 10.1248/yakushi1947.119.6_417.
The purinergic modulation of the release of norepinephrine (NE) from sympathetic nerves in the rabbit ear artery was investigated. Methoxamine, an alpha 1-adrenoceptor agonist, enhanced the NE-release by electrical stimulation (ES) and released large amounts of adenyl purines (ATP, ADP, AMP and adenosine) from the endothelium. Both actions of methoxamine were blocked by prazosin. In addition, the enhancement of the NE-release by methoxamine was abolished by 8-sulfophenyl theophylline (8SPT), a P1-Purinoceptor antagonist. These findings indicated that the endogenous purines and purinoceptors participate in the facilitation of NE-release by alpha 1-adrenoceptor stimulation. P1-Purinoceptor agonists, such as adenosine and 2-chloroadenosine, and P2-purinoceptor agonists, such as ATP and beta,gamma-methylene ATP (beta gamma-mATP), enhanced the ES-evoked NE-release. This enhancement was antagonized not only by the P1-purinoceptor antagonist, 8SPT, but also by the P2-purinoceptor desensitizing agent, alpha,beta-methylene ATP. A phosphodiesterase inhibitor, Ro20-1724 potentiates the enhancement of NE-release by beta gamma-mATP. On the other hand, an adenylate cyclase inhibitor, SQ22536, inhibited the enhancement of NE-release by beta gamma-mATP. These findings suggested that prejunctional facilitatory purinoceptors exist on the adrenergic nerves of the rabbit ear artery. This receptor may be coupled to adenylate cyclase and is different from well-known P1 and P2 purinoceptors. In the rabbit ear artery, adrenergic neurotransmission may be regulated by endogenous ATP and its metabolites via prejunctional facilitatory purinoceptors, which were initiated by alpha 1-adrenoceptor stimulation; i.e. transsynaptic regulation of neurotransmission.
研究了嘌呤能对兔耳动脉交感神经去甲肾上腺素（NE）释放的调节作用。α1肾上腺素受体激动剂甲氧明可增强电刺激（ES）引起的NE释放，并从内皮细胞释放大量腺苷嘌呤（ATP、ADP、AMP和腺苷）。甲氧明的这两种作用均被哌唑嗪阻断。此外，P1嘌呤受体拮抗剂8-磺苯基茶碱（8SPT）可消除甲氧明对NE释放的增强作用。这些发现表明内源性嘌呤和嘌呤受体参与了α1肾上腺素受体刺激促进NE释放的过程。P1嘌呤受体激动剂，如腺苷和2-氯腺苷，以及P2嘌呤受体激动剂，如ATP和β,γ-亚甲基ATP（βγ-mATP），均可增强ES诱发的NE释放。这种增强不仅被P1嘌呤受体拮抗剂8SPT拮抗，也被P2嘌呤受体脱敏剂α,β-亚甲基ATP拮抗。磷酸二酯酶抑制剂Ro20-1724可增强βγ-mATP对NE释放的增强作用。另一方面，腺苷酸环化酶抑制剂SQ22536可抑制βγ-mATP对NE释放的增强作用。这些发现提示兔耳动脉肾上腺素能神经上存在突触前促进性嘌呤受体。该受体可能与腺苷酸环化酶偶联，且不同于已知的P1和P2嘌呤受体。在兔耳动脉中，肾上腺素能神经传递可能通过突触前促进性嘌呤受体受内源性ATP及其代谢产物的调节，这种调节由α1肾上腺素受体刺激引发；即神经传递的跨突触调节。
