Abstract:The effects of different loading procedures on norepinephrine-3H (NE-3H) efflux induced by a structurally analogous group of indirectly acting sympathomimetic amines was examined in rabbit vas deferens. (+)-Amphetamine was ineffective in releasing 3H from tissues with intact intraneuronal storage granules but was an effective depletor of (a) non-granular intraneuronal compartment(s) following in vivo treatment with reserpine. (±)-p-Hy-droxynorephedrine was a less effective depl… Show more
“…Alternative reasons for the apparent insensitivity of the guinea-pig vas deferens have been put forward, for example, the existence of tyramine-insensitive pools of NA (Takimoto, Amiri & Cho, 1981). The present findings do not support such a theory, since in this study tyramine significantly enhanced the release of [3H]-NA.…”
1. Adenosine 5'triphosphate (ATP) as well as [3H]-noradrenaline ([3H]-NA) is released by perfusion of the vas deferens with the indirect sympathomimetic tyramine (100 microM); this result is consistent with the concept of sympathetic cotransmission. 2. While tyramine produced a strong contraction in the vas deferens of the rat, it had little mechanical action in the guinea-pig vas deferens. This appears to be largely because tyramine induces considerably lower levels of release of both ATP and NA from the guinea-pig vas deferens compared to that of the rat. Furthermore, NA released by tyramine appears to release ATP from a secondary pool in the rat vans deferens, but not that of the guinea-pig, since prazosin reduced the tyramine-induced release of ATP in the rat vas deferens. 3. alpha,beta-Methylene ATP (alpha,beta-meATP) increased both the spontaneous release of ATP and the tyramine-evoked efflux of ATP and [3H]-NA. The basal and tyramine-induced efflux of [3H]-NA was also enhanced by the alpha 1-adrenoceptor antagonist, prazosin, suggesting that prejunctional alpha 1-adrenoceptors may modulate neurotransmitter release.
“…Alternative reasons for the apparent insensitivity of the guinea-pig vas deferens have been put forward, for example, the existence of tyramine-insensitive pools of NA (Takimoto, Amiri & Cho, 1981). The present findings do not support such a theory, since in this study tyramine significantly enhanced the release of [3H]-NA.…”
1. Adenosine 5'triphosphate (ATP) as well as [3H]-noradrenaline ([3H]-NA) is released by perfusion of the vas deferens with the indirect sympathomimetic tyramine (100 microM); this result is consistent with the concept of sympathetic cotransmission. 2. While tyramine produced a strong contraction in the vas deferens of the rat, it had little mechanical action in the guinea-pig vas deferens. This appears to be largely because tyramine induces considerably lower levels of release of both ATP and NA from the guinea-pig vas deferens compared to that of the rat. Furthermore, NA released by tyramine appears to release ATP from a secondary pool in the rat vans deferens, but not that of the guinea-pig, since prazosin reduced the tyramine-induced release of ATP in the rat vas deferens. 3. alpha,beta-Methylene ATP (alpha,beta-meATP) increased both the spontaneous release of ATP and the tyramine-evoked efflux of ATP and [3H]-NA. The basal and tyramine-induced efflux of [3H]-NA was also enhanced by the alpha 1-adrenoceptor antagonist, prazosin, suggesting that prejunctional alpha 1-adrenoceptors may modulate neurotransmitter release.
“…Graduate students Glenn Takimoto and Joseph Fischer studied the Amp-based efflux of norepinephrine from preloaded sympathetically innervated tissues (37,38) and brain synaptosomes (39,40). Based on the results of these studies, we proposed an exchange diffusion-based model for Amp-induced catecholamine efflux from nerve terminals (34).…”
My chemical training provided a somewhat different perspective of biological problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.
“…To address the relevance of the Amp and phentermine metabolic pathways to their neurochemistry, the biological component of our laboratory began studies on the catecholaminergic nerve terminal as the target of the Amp class of compounds. Graduate students Glenn Takimoto and Joseph Fischer studied the Amp-based efflux of norepinephrine from preloaded sympathetically innervated tissues (37,38) and brain synaptosomes (39,40). Based on the results of these studies, we proposed an exchange diffusion-based model for Amp-induced catecholamine efflux from nerve terminals (34).…”
My chemical training provided a somewhat different perspective of biological problems, in the problem itself and approaches to its solution. I was fortunate to have in my laboratory postdocs and students who shared this perspective and used appropriate tools to address problems in amphetamine pharmacology and air pollution toxicology. These apparently disparate areas of research shared two chemical reactions: prooxidant-based generation of reactive oxygen and formation of covalent bonds between electrophiles and biological nucleophiles. This article is an attempt to summarize that research and to identify those individuals who made the contributions.
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