Reference

Sodium dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens

Sodium dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens. Zeitner, C. J.; Graefe, K. H. (Inst. Pharmakol. Toxikol., Univ. Wuerzburg, Wuerzburg D-8700, Fed. Rep. Ger.). Naunyn-Schmiedeberg's Arch. Pharmacol., 334(4), 397-402 (English) 1986. CODEN: NSAPCC. ISSN: 0028-1298. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Vasa deferentia obtained from reserpine-pretreated rats were incubated in media contg. monoamine oxidase and catechol O-methyltransferase inhibitors and various concns. of 3H-labeled (-)-noradrenaline [51-41-2] and Na+, and initial rates of the neuronal uptake of [3H]noradrenaline were measured both in the absence and presence of uptake inhibitors after 1 min of incubation. When rates of uptake were detd. at various [3H]noradrenaline (1.0-12.2 mM) and 2 fixed Na+ concns. (25 and 140 mM), the inhibition of uptake produced by (+)-amphetamine [51-64-9], (-)-metaraminol bitartrate [33402-03-8], desipramine [50-47-5], nomifensine hydrogen maleate [32795-47-4], and cocaine [50-36-2] was competitive with respect to [3H]noradrenaline at both Na+ concns. Whereas the Ki for (+)-amphetamine, (-)-metaraminol, desipramine and nomifensine increased when the Na+ concn. was lowered, that for cocaine decreased. When the Na+ concn. was varied (10-140 mM) and the noradrenaline concn. held const. (1.2 mM), (+)-amphetamine, (-)-metaraminol, nomifensine, and desipramine acted as mixed-type inhibitors with respect to Na+, and the inhibition of uptake produced by these drugs was the more pronounced, the higher the Na+ concn. On the other hand, cocaine was competitive with Na+ and the inhibition produced by this drug was the more pronounced, the lower the Na+ concn. Apparently, the inhibitors of neuronal uptake tested here act in dependence on the external Na+ concn. Desipramine and nomifensine resemble alternative amine substrates in being more potent at high than at low Na+ concns. On the other hand, cocaine is more potent at low than at high Na+ concns.

The effects of prostaglandin perfusion on the vascular responses to nerve stimulation and sympathomimetic amines

The effects of prostaglandin perfusion on the vascular responses to nerve stimulation and sympathomimetic amines. George, A. J. (Sch. Pharm., Liverpool Polytech., Liverpool, Engl.). Pharmacol. Res. Commun., 9(4), 397-414 (English) 1977. CODEN: PLRCAT. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) Section cross-reference(s): 1 The effects of prostaglandins E1 (I) [745-65-3], E2 [363-24-6], and F2.alpha. [551-11-1] on the response of the perfused rat mesentery artery to nerve stimulation and sympathomimetic amines were investigated. I, E2, and F2.alpha. inhibited responses to sympathetic nerve stimulation maximally at a perfusion concn. of 10 mg/mL. Responses to tyramine [51-67-2], octopamine-HCl [4502-14-1], noradrenaline-HCl [329-56-6], and metaraminol bitartrate [33402-03-8] were inhibited maximally at 100 ng/mL. The most potent inhibitor was I, and the greatest percentage inhibition (67%) was in the presence of tyramine. Indomethacin had no effect on responses to sympathomimetic amines. It is concluded that PGs have a role in the release of noradrenaline by nerve stimulation and by sympathomimetic amines.