Purinergic modulation of vascular sympathetic neurotransmission.
It is generally agreed that the release of norepinephrine (NE) is inhibited by activation of prejunctional purinoceptor. We examined the pharmacological properties of purinoceptors on vascular sympathetic nerve terminals and the source of endogenous adenyl purines. Electrically (1 Hz) evoked NE-release was inhibited by not only P1-agonists but also P2-agonists. Although the inhibition induced by P2-agonists was blocked by P1-antagonists, P2-agonists-induced inhibition was not due to the breakdown to adenosine. Therefore, there may be a new class of purinoceptor that is activated by both P1- and P2-agonists and antagonized by P1-antagonists. Electrical stimulation at 8 Hz but not at 1 Hz evoked the release of adenyl purines such as ATP, ADP, AMP and adenosine, in addition to NE; and the purines-release was blocked by an alpha1-antagonist. Methoxamine, an alpha1-agonist, also evoked the release of purines. Electrically (1 Hz)-evoked NE-release was inhibited by methoxamine, and this inhibition was blocked by not only an alpha1-antagonist but also a P1-antagonist. Therefore, the activation of alpha1-adrenoceptor appeared to release purines, which in turn inhibited NE-release via prejunctional purinoceptors. From these results, it is suggested that the unique purinoceptor and the endogenous purines released from alpha1-adrenoceptor-sensitive sources participate in the antidromic transsynaptic modulation of vascular sympathetic neurotransmission.
Shinozuka
Kazumasa
K
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women 's University, Nishinomiya, Japan. kazumasa@mwu.mukogawa-u.ac.jp
Mizuno
Hideya
H
Nakamura
Kazuki
K
Kunitomo
Masaru
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D004594:Electrophysiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011687:Purines / Q000378:metabolism / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013623:Tail / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D011687:Purines; D011799:Quinazolines; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; C018176:bunazosin; D009638:Norepinephrine