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J M Barbosa-Filho

Publications and source records attributed to J M Barbosa-Filho.

24 records · Page 2Linked to original sources
PubMed1997

Pharmacological evidence for the putative existence of two different subtypes of PAF receptors on platelets and leukocytes; studies with yangambin.

Yangambin, a new naturally-occurring platelet activating receptor (PAF) receptor antagonist competitively displaced [3H]-PAF from its high affinity binding sites on washed human platelets with a Ki value of 1.1 +/- 0.3 microM (n = 3). Studies carried out in parallel demonstrated that SR 27417, a newly-developed PAF receptor antagonist also antagonized [3H]-PAF binding to these cells with a Ki value of 51 +/- 2 pM. SR 27417 (N-(2-dimethylamino ethyl)-N-(3-pyridinyl methyl) [4-(2,4,6-triisopropyl phenyl) thiazol-2-yl] amine) selectively and competitively inhibited the specific binding of [3H]-PAF on human polymorphonuclear leukocytes (Ki = 65 +/- 5.2 pM) whereas high doses of yangambin remained ineffective. Yangambin inhibited PAF-induced aggregation of human platelets in vitro (IC50 = 1.0 +/- 0.2 microM) but had no effect PAF-induced oxidative burst in human polymorphonuclear leukocytes. In guinea pigs, yangambin inhibited PAF-induced thrombocytopenia but did not affect leukocytopenia whereas SR 27417 afforded complete protection against both PAF-induced thrombocytopenia and leukocytopenia. In conclusion, yangambin discriminates between two different types of PAF receptors on platelets and polymorphonuclear leukocytes and can be considered as the first PAF receptor antagonist described to date exhibiting such an effect.

Animals↗
PubMed1997

Anti-allergic properties of the natural PAF antagonist yangambin.

In this study we examined the ability of the furofuran lignan yangambin to influence the local and systemic responses induced by antigen or PAF in actively sensitized or normal rats. Given intraperitoneally 1 h before stimulation, yangambin inhibited the pleural neutrophil and eosinophil infiltration evoked by the i.pl. injection of PAF or antigen into normal or 14 daysensitized rats whereas plasma exudation evoked by both stimuli was unaffected. The pleural neutrophil influx (6 h) after LTB4 stimulation was also significantly inhibited by yangambin. We also evidenced that the hemoconcentration, thrombocytopenia, and leucocytosis noted after i.v. PAF were all attenuated by yangambin. In actively sensitized rats, pretreatment with yangambin failed to modify the antigen-induced hemoconcentration and leucocytosis, but dose-dependently abrogated the thrombocytopenia noted 1 h post-stimulation. In vitro, the anaphylactic contraction of longitudinal jejunal segments to antigen challenge was significantly inhibited by yangambin (10(-5)-10(-4) M). Likewise, the contraction of jejunal segments from normal rats to PAF was markedly blocked by yangambin under conditions where the response to 5-hydroxytryptamine (5-HT) was not altered. In conclusion, our results show that antigen- and PAF-induced pleural neutrophil and eosinophil accumulation, but not exudation, is sensitive to treatment with yangambin. In addition, yangambin also suppressed the pleural neutrophil infiltration triggered by LTB4 as well as the blood thrombocytopenia and intestinal anaphylaxis elicited by antigen in rats. Thus, our findings indicate that yangambin shows an antagonistic action on receptors other than those of PAF, i.e., LTB4, and strongly suggest that it may be a useful drug in the treatment of some allergic inflammatory responses.

Animals↗
PubMed1995

Yangambin: a new naturally-occurring platelet-activating factor receptor antagonist: binding and in vitro functional studies.

The effects of the furofuran lignan yangambin on rabbit platelet aggregation and binding of [3H]-PAF to rabbit platelet plasma membranes were studied. Log concentration-response curves to PAF were obtained in the presence or absence of increasing concentrations of yangambin. This lignan dose-dependently inhibited PAF-induced platelet aggregation in platelet-rich plasma (PRP) and shifted PAF curves to the right without decreasing the maximal response. The Schild plot constructed from these data showed a slope of 1.17 and a pA2 of 6.45. Moreover, yangambin at 10(-5) M did not inhibit the platelet aggregation induced by ADP (5 x 10(-7) M), collagen (0.1 microgram ml-1), or thrombin (0.05 U ml-1). Biochemical studies showed that [3H]-PAF labelled in a saturable manner a single class of binding sites on platelet membranes with a Kd of 1.25 +/- 0.24 nM and a maximal binding capacity (Bmax) of 14.9 +/- 2.4 pmol mg protein-1. Both unlabelled PAF and yangambin competitively displaced [3H]-PAF binding with an IC50 of 1.54 +/- 0.37 nM and 1.93 +/- 0.53 microM, respectively. The incubation of rabbit blood neutrophils with yangambin at 10(-5) M did not prevent PAF-induced in vitro chemotaxis in conditions where the PAF antagonist SR 27417 at 10(-5) M abolished the phenomenon. These results indicate that yangambin is an antagonist that selectively blocks PAF receptors on platelets.

Animals↗
PubMed1995

Yangambin: a new naturally-occurring platelet-activating factor receptor antagonist: in vivo pharmacological studies.

The pharmacological profile of a novel specific platelet-activating factor (PAF) receptor antagonist-yangambin-isolated from the Brazilian plant Ocotea duckei Vattimo (Lauraceae), was investigated in the pentobarbitone-anaesthetized rabbit. The i.v. administration of PAF (0.03-3.0 microgram kg-1) induced marked but reversible hypotensive effects and mild reductions in the heart rate. Both effects are independent of the respiratory conditions imposed on the animals. Moreover, PAF (3.0 microgram kg-1, i.v.) induced a reversible decrease of the circulating levels of platelets and of polymorphonuclear leukocytes. Pretreatment with yangambin (10 and 20 mg kg-1, i.v.) dose-dependently attenuated PAF-induced cardiovascular changes and thrombocytopaenia. Nevertheless, the neutropenic leukopaenia elicited by PAF (3.0 microgram kg-1, i.v.) was not prevented by yangambin whereas the reference PAF antagonists WEB 2086 (2 mg kg-1, i.v.) and SR 27417 (1 mg kg-1, i.v.) significantly inhibited the phenomenon. The hypotensive effects of acetylcholine, histamine, and 5-hydroxytryptamine were not affected by prior administration of yangambin. It is concluded that yangambin is a selective antagonist of the cardiovascular effects of PAF which could be useful in pathological states characterized by abnormal PAF release, such as anaphylactic and septic shocks. Furthermore, yangambin might discriminate a PAF receptor subtype present in the cardiovascular system and platelets from the one existing in polymorphonuclear leukocytes in the rabbit.

Animals↗
PubMed1991

Chemical and pharmacological investigation of Solanum species of Brazil--a search for solasodine and other potentially useful therapeutic agents.

A systematic search for solasodine, an important starting material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliflorum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showed curare like activity yielded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yielded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and excitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity.

Anti-Infective Agents↗