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.
Castro-Faria-Neto
H C
HC
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Araújo
C V
CV
Moreira
S
S
Bozza
P T
PT
Thomas
G
G
Barbosa-Filho
J M
JM
Cordeiro
R S
RS
Tibiriçá
E V
EV
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D010944:Plants / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001381:Azepines; D005663:Furans; D017705:Lignans; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C082827:epiyangambin; C071317:Foropafant