[Characterization of the facilitatory modulation of adrenergic neurotransmission via prejunctional purinoceptors in rabbit ear artery].
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.
Ishii-Nozawa
R
R
Meiji Pharmaceutical University, Kiyose, Japan.
Shinozuka
K
K
Kunitomo
M
M
Takeuchi
K
K
Hashimoto
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000294:innervation; D004423:Ear / Q000098:blood supply*; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D058914:Purinergic Antagonists; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D008729:Methoxamine; D009638:Norepinephrine