Indications for vascular alpha- and beta-2 adrenoceptors in synapses of the muscarinic pathway in the pithed normotensive rat.

In the pithed normotensive rat the adrenoceptors involved in the hypertensive and tachycardic effects of the indirectly acting sympathomimetic agent tyramine and of electrical stimulation of the spinal cord (TH5-L4 or C7-Th1) were analyzed. The tools used for the identification of the adrenoceptors were the selective alpha-1 adrenoceptor blocking drug prazosin, the selective alpha-2 adrenoceptor antagonist rauwolscine, the beta-1 blocker atenolol and the selective beta-2 adrenoceptor blocking agent ICI 118,551. The participation of vascular alpha-2 adrenoceptors in the pressor response of tyramine was shown.

Differential effects of selective alpha 1- and alpha 2-adrenoceptor agonists on intraocular pressure in the conscious rabbit.

In the present study the influence of topically applied selective alpha 1- and alpha 2-adrenoceptor agonists on intraocular pressure and the diameter of the pupil was investigated in conscious rabbits. Selective stimulation of the alpha 1-subtype of receptors induced an elevation in intraocular pressure, accompanied by mydriasis, whereas stimulation of the alpha 2-subtype caused a marked and dose-dependent ocular hypotensive response, which could be blocked by the selective alpha 2-adrenoceptor antagonist yohimbine. After application of the non-selective alpha-adrenoceptor agonist clonidine the alpha 2-adrenoceptor mediated decrease in IOP is probably counteracted by a pressor effect due to the stimulation of alpha 1-adrenoceptors.

Central and peripheral alpha-adrenoceptors.

The recent interest in the characterization and functional, role of alpha-adrenoceptors has prompted us to study the following different, although interdigitated, lines of research: (a) The functional role of calcium ions in the process of vasoconstriction, induced by alpha 2-adrenoceptor stimulation. We have shown in various animal species that the vasoconstriction induced by alpha 2-adrenoceptor stimulation with specific agonists is impaired by various organic and inorganic calcium antagonists. This finding suggests that the influx of extracellular calcium is required in order to enable the occurrence of vasoconstriction, mediated by the stimulation of vascular alpha 2-adrenoceptors.

A comparison of peripheral pre- and postsynaptic alpha 2-adrenoreceptors using meta-substituted imidazolidines.

1 The cardiac presynaptic activity, as derived from the inhibition of tachycardia to electrical stimulation of the cardiac sympathetic nerve in pithed, normotensive rats of 8 meta-substituted phenyl(imino)imidazolidines (2, 3- and 2,5- derivation) was determined. 2 The agonistic activity of the imidazolidines was measured with respect to vascular alpha 1- and alpha 2-adrenoreceptors. Accordingly, the increase in diastolic pressure of pithed, normotensive rats to intravenous administration of the imidazolidines was evaluated after pretreatment with 5% w/v glucose solution, yohimbine (1 mg/kg), prazosin (0.

The effect of selective alpha 1- and alpha 2-adrenoceptor stimulation on intraocular pressure in the conscious rabbit.

The influence of topically applied selective alpha 1-and alpha 2-adrenoceptor agonists on intraocular pressure and the diameter of the pupil was investigated in conscious rabbits. Selective stimulation of the alpha 1-subtype of receptors induced an elevation in intraocular pressure, accompanied by mydriasis, whereas stimulation of the alpha 2-subtype caused a marked and dose-dependent ocular hypotensive response, which was blocked by the selective alpha 2-adrenoceptor antagonist yohimbine. alpha 2-Agonists induced neither macroscopic ocular side effects, nor an effect on the pupil size.

Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic alpha 2-adrenoceptors.

The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective alpha 1-adrenoceptor agonist methoxamine and the selective alpha 2-adrenoceptor stimulating agent B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) was studied in pithed rats. 1. The calcium antagonists verapamil, D 600 and nifedipine, when given intraarterially (i.

Discrimination between peripheral and central alpha-adrenergic effects using meta-substituted imidazolidines.

meta-Substituted 2-chlorophenyl(imino)imidazolidines of the clonidine-type (2,3- and 2,5-substituted derivatives) were used in attempts to discriminate between alpha-adrenergic effects (central hypotensive and peripheral hypertensive activities) in rats. The central hypotensive activity of four pairs of substitution isomers was expressed as a pC20, calculated from log dose-response curves after i.v.

Characterization of alpha-adrenoceptor populations. Quantitative relationships between cardiovascular effects initiated at central and peripheral alpha-adrenoceptors.

The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alpha-adrenoceptors for 21 structurally dissimilar alpha-adrenoceptor agonists. Hypotensive potency after intravenous administration to anesthetized, normotensive rats was determined as a measure of central alpha-adrenergic activity and expressed as pC25, obtained from log dose-response curves.

Vascular smooth muscle contraction initiated by postsynaptic alpha 2-adrenoceptor activation is induced by an influx of extracellular calcium.

Vasoconstriction in pithed, normotensive rats elicited via stimulation of postsynaptic alpha 2-adrenoceptors by B-HT 920 was antagonized by EDTA and the calcium antagonists nifedipine, D 600 and verapamil, whereas pressor responses to the alpha 1-agonist methoxamine were unaffected. This indicates that vasoconstriction in vivo initiated via postsynaptic alpha 2-adrenoceptors requires an influx of extracellular calcium. Thus, the antihypertensive effect of calcium antagonists may be based upon a diminution of vascular tone maintained by postsynaptic alpha 2-adrenoceptors.

Factors affecting the hydrolysis of ceramide-3 by alpha-galactosidase A from human liver.

1. The effect of detergents on the catalytic properties of alpha-galactosidase from human liver was studied using p-nitrophenyl-alpha-galactoside and galactosyl-alpha(1 leads to 4)-galactosyl-beta(1 leads to 4)-glucosylceramide (ceramide-3) as substrates. 2.

Properties of immobilized fig alpha-galactosidase and effect on ceramide-3 content of plasma from patients with Fabry's disease.

The possibility of lowering the level of ceramide-3 (galactosyl-alpha(1 leads to 4)-galactosyl-beta(1 leads to 4)-glucosyl-beta(1 leads to 1)-ceramide) in the plasma of patients with Fabry's disease was investigated. An immobilized alpha-galactosidase (alpha-D-galactoside galactohydrolase, EC 3.2.

An enrichment technique for auxotrophs of Agrobacterium tumefaciens using a combination of carbenicillin and lysozyme.

A procedure to enrich for auxotrophic and fermentation mutants of Agrobacterium tumefaciens is described. The method is based on the amplification of the killing power of carbenicillin by the addition of lysozyme. Isolation frequencies of some types of mutants are presented, with and without the application of the proposed procedure.