Search PubMed⌕ Search

Biomedical subjects

A G Herman

Publications and source records attributed to A G Herman.

282 records · Page 16Linked to original sources
PubMedDate not supplied

Stereochemical considerations in relation to the pharmacological activity of Pterotaberna alkaloids.

Five 2-acylindole alkaloids, isolated from the leaves of Pterotaberna inconspicua, were pharmacologically investigated. The major alkaloids methuenine and 16-epimethuenine showed some interesting pharmacological features, whereas the minor alkaloids including 6-oxomethuenine and methuenine N-oxide were almost devoid of these pharmacological properties. Methuenine, being the most potent, was characterized as a non competitive antagonist against acetylcholine (pD'2=5.10 +/- 0.11) and histamine (pD'2 = 5.13 +/- 0.14) in guinea-pig ileum. Its potency was comparable to that of papaverine. 16-Epimethuenine behaved as a weak antihistaminic (pA2 = 6.55 +/- 0.08). The stereochemistry of both components is discussed in relation to their pharmacological activity.

Alkaloids↗
PubMedDate not supplied

In vitro effects of tremorgenic mycotoxins.

Paxilline was isolated from Penicillium paxilli (NRRL 6110). It was studied together with penitrem B and verruculogen in the electrically stimulated guinea pig ileum. All three mycotoxins enhanced the electrically induced twitch contractions, without influencing the contractions provoked by exogenous acetylcholine. The effect of the mycotoxins could be greatly diminished by hyoscine. The possible mechanism of action of these substances in this in vitro model is discussed. The electrically stimulated guinea pig ileum could be useful in the detection and estimation of the biological activity of tremorgenic mycotoxins.

Acetylcholine↗
PubMedDate not supplied

Histamine levels in stored platelet concentrates. Relationship to white cell content.

The histamine levels in samples from platelet concentrates (PC) were measured at various storage times by a radioenzymatic assay. Elevated histamine levels were detected in 5 of 14 PC after 3 days of storage (range, less than 1 to 13.3 ng/ml) and in 9 of 14 PC after 5 days (range, less than 1 to 22.2 ng/ml). A very good linear correlation (r = 0.913) was found between the initial white cell content of the PC and the histamine level at 5 days of storage. The rise in histamine content was not influenced by the type of plastic container. The results indicate a process of histamine release by the white cells during storage. Although histamine is metabolized rapidly in vivo, a critical histamine threshold could be reached in man by the rapid infusion of stored PC containing high levels of histamine. This could explain some unexpected transfusion reactions in patients receiving PC.

Blood Platelets↗
PubMedDate not supplied

Effects of prostacyclin on contractile properties of isolated mammalian cardiac muscle.

We studied the influence of prostacyclin (PGI2) on the contractile performance of isolated mammalian ventricular muscle. PGI2 had no direct influence on myocardial contractility, as evidenced by experiments on single cardiac cells and papillary muscle. Moreover, PGI2 did not interfere with the inotropic action of isoproterenol. In comparison, neither prostaglandin E1 nor E2 appeared to have any cardiotonic action.

Alprostadil↗
PubMedDate not supplied

Evidence for a differential release of nitric oxide and vasoactive intestinal polypeptide by nonadrenergic noncholinergic nerves in the rat gastric fundus.

The roles of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) in nonadrenergic noncholinergic (NANC) nerve-mediated relaxations were investigated in longitudinal muscle strips of the rat gastric fundus. Transmural stimulation (1-16 Hz for 2 min), VIP and noradrenaline evoked a prolonged relaxation of the rat gastric fundus, whereas NO evoked a transient relaxation. Only the electrically induced responses were blocked by tetrodotoxin. The inhibitor of NO biosynthesis NG-nitro-L-arginine (L-NNA) preferentially inhibited the relaxations induced by low frequency stimulation. In contrast, trypsin mainly reduced the electrically induced relaxations to high frequency stimulation; the NANC relaxations resistant to trypsin were further inhibited by L-NNA. VIP-induced relaxations were abolished by trypsin, but remained unaffected by L-NNA. NO- or noradrenaline-induced relaxations were not inhibited by either L-NNA or trypsin alone, whereas the combination of L-NNA and trypsin slightly reduced the noradrenaline-induced responses. These results suggest that NANC responses in the rat gastric fundus at low frequency are mediated mainly by NO, whereas at higher frequency NO together with a peptide, probably VIP, are released.

Animals↗
PubMedDate not supplied

Influence of clomipramine and embolization on the characterization of serotonin uptake in rabbit lung using a new mathematical model.

The kinetic parameters Vmax and Km of the carrier-mediated uptake of serotonin by the lung can be used as an index of endothelial distress. To this purpose we have recently developed a new mathematical model which estimates the kinetic parameters of the double uptake mechanism of serotonin by the rabbit lung (MODEL3, Peeters et al., 1989). The aim of the present study was to evaluate the behavior of this new model after inhibition of the uptake by clomipramine and after reduction of the perfused lung surface with glass bead embolization. Clomipramine administration did not cause distinct hemodynamic alterations, but decreased the serotonin extraction and Vmax/Km (the sum of all first order rate constants). After clomipramine, Vmax1, i.e., the maximal velocity for the first uptake pathway, was significantly decreased, while Km1 tended to increase without reaching significance. The virtual inhibition constant of clomipramine was about 1 microM. Glass bead embolization resulted in large hemodynamic responses, decreased extraction of serotonin and decreased values for Vmax/Km and Vmax1. This is consistent with a diminished vascular surface available for serotonin extraction. We conclude that MODEL3 was able to detect changes in intrinsic uptake capacity and vascular surface area, which were especially reflected in a decrease of Vmax/Km and Vmax1.

Animals↗
PubMedDate not supplied

Prejunctional beta-adrenoceptors in the isolated perfused rat kidney: a comparative study of the beta-blockers tertatolol and propranolol.

The interaction of the beta-blocker tertatolol with the prejunctional beta-adrenoceptors of the rat renal vasculature was examined. In isolated Tyrode-perfused rat kidneys isoproterenol (5 x 10(-7) M to 2 x 10(-6) M) slightly decreased the pressor responses to noradrenaline (0.5 nmol), but markedly increased those to electrical stimulation (6 Hz). Tertatolol at 3 x 10(-7) M inhibited both effects of isoproterenol. Electrical stimulation (6 Hz) caused an overflow of intact 3H-noradrenaline from kidneys previously labelled with the 3H-transmitter; this stimulation-induced release was augmented by isoproterenol. Also this effect of isoproterenol was prevented by 3 x 10(-7) M of tertatolol. In different groups of rat kidneys labelled with 3H-noradrenaline, isoproterenol (5 x 10(-7) M) augmented the stimulation (1 Hz), induced 3H overflow and this increased transmitter output was concentration-dependently inhibited by tertatolol and propranolol; from the IC50 values it was calculated that tertatolol was 16 times more potent than propranolol. Even at concentrations up to 10(-5) M, neither tertatolol nor propranolol significantly altered the basal and stimulation-induced transmitter release from the rat kidneys. From the data we conclude that tertatolol is a powerful inhibitor of the prejunctional beta-adrenoceptors in the renal circulation of the rat. Stimulation of these receptors by beta-agonists not only enhances transmitter release but also increases the pressor responses induced by electrical stimulation.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Interaction of rilmenidine and clonidine with pre- and postjunctional alpha-adrenoceptors in rat and rabbit blood vessels and in rat kidneys.

In several blood vessels, the influence of the alpha 2-adrenoceptor agonists rilmenidine and clonidine was compared. In aortas of rat and rabbit and in the rabbit pulmonary artery, both compounds evoked contractions due to stimulation of postjunctional alpha 1-adrenoceptors. In the aorta of the rat, but not in that of the rabbit, removal of the endothelium markedly enhanced the contractions to rilmenidine and clonidine. At the alpha 1-adrenoceptors, clonidine was about 135 times more potent than rilmenidine. The activity of both substances at post- and prejunctional alpha 2-adrenoceptors was compared in the rabbit saphenous vein. Rilmenidine and clonidine evoked contractions of the vein by stimulating postjunctional alpha 2-adrenoceptors and decreased the stimulation-induced overflow of [3H]-noradrenaline by activating the prejunctional alpha 2-adrenoceptors. At the post- and prejunctional alpha 2-adrenoceptors, clonidine was about 30 times more potent than rilmenidine. These data illustrate that, although less potent than clonidine, rilmenidine is 5 times more specific for the alpha 2-adrenoceptors. In the isolated perfused rat kidney, rilmenidine and clonidine antagonized the vasoconstrictions induced by noradrenaline. Although the exact mechanism of this inhibitory response remains to be elucidated, our results indicate that rilmenidine may possess some interesting properties at the level of the renal circulation.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Bioassay and pharmacological characterization of the nitrergic neurotransmitter.

Based on organ bath experiments illustrating nitric oxide (NO) or an NO-releasing substance as mediator of the nonadrenergic noncholinergic (NANC) nerve-induced relaxations in the canine ileocolonic junction and rat gastric fundus, a bioassay superfusion technique was developed to detect and characterize the inhibitory NANC neurotransmitter. Evidence is provided that NANC nerve stimulation results in the release of a vasorelaxant factor with pharmacological properties similar to NO: its release is blocked by inhibition of the NO biosynthesis and tetrodotoxin, but enhanced by L-arginine. Its half-life is comparable to that of NO, and its biological activity is enhanced by superoxide dismutase, but abolished by hemoglobin. In addition, the nitrergic transferable factor is similarly affected as authentic NO by pyrogallol, hydroquione, hydroxocobalamin and L-cysteine. Nitrosothiols, like S-nitroso-L-cysteine, S-nitrosoglutathione and S-nitroso-N-acetyl-D,L- penicillamine, on the other hand, have a different pharmacological profile compared to NO and the nitrergic factor, indicating that NO, and not a nitrosothiol, is released from inhibitory NANC nerves in the canine ileocolonic junction. This nerve-induced release is Ca(2+)-dependent and prejunctionally regulated by K+ channels and alpha 2-adrenoceptors: blockade of K+ channels enhances the release, whereas alpha 2-adrenoceptor activation reduces the release of the nitrergic factor, possibly by activating K+ channels.

Animals↗
PubMedDate not supplied

Effects of enantiomers of M3 antagonists on muscarinic receptors in rabbit trachea.

The effects of the enantiomers of structurally related chiral M3 antagonists (trihexyphenidyl, p-fluorohexahydrodifenidol, hexahydrodifenidol and p-fluorohexbutinol) were studied at the presynaptic M2 and postsynaptic M3 receptor level in the rabbit trachea. All isomers were M3- over M2-selective as they did not increase the release of acetylcholine (an M2 effect) at concentrations that significantly inhibited smooth muscle contraction (an M3 effect). At the smooth muscle receptor, the R-enantiomers were consistently more potent than the S-enantiomers. The potency ratios (IC50(S)/IC50(R)) varied from 6 for p-fluorohexbutinol to 288 for trihexyphenidyl, and increased with higher eutomer potencies, in accordance to Pfeiffer's rule. Furthermore, we found that the potency of the racemic mixture of hexahydrodifenidol was significantly lower than that of the eutomer R-hexahydrodifenidol. To exclude that this difference was due to the lower concentration of the more active isomer, present in a racemic mixture, we calculated the potencies (-log IC50 values) of mixtures of the isomers of hexahydrodifenidol with varying amounts of S-hexahydrodifenidol and a constant amount of R-hexahydrodifenidol. We found that the presence of the distomer altered the potency of the eutomer in a dose-related manner. In conclusion, we have shown that the muscarinic smooth muscle receptor can be blocked differentially by the isomers of muscarinic antagonists and that the presence of the less active compound alters the potency of the most active isomer. We, therefore, suggest that, in bronchodilating therapy, the use of the pure eutomer might have advantages.

Acetylcholine↗