A study of prostacyclin mimetics distinguishes neuronal from neutrophil IP receptors.
The prostacyclin mimetics BMY 45778 (3-[4-(4,5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy]acetic acid), BMY 42393 (2-[3-[2-(4,5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid) and EP 185 (rac 5-endo-(6'-carboxyhex-2'Z-enyl)-6-exo-(p-methoxyphenyl- phenyl-methylazino)-bicyclo[2.2.2]oct-2-ene) inhibited rat neutrophil aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine (IC50 = 20, 462, and 1195 nM respectively). In contrast only BMY 45778 (1-10 microM) produced any significant inhibition (10-20%) of the spontaneous activity of rat colon. BMY 45778 (10 microM) also attenuated the inhibitory effect of the prostacyclin analogue cicaprost on rat colon, whereas BMY 42393 and EP 185 did not. BMY 45778 appears to be a low affinity partial agonist at prostacyclin receptors on rat colon and its low potency in rat colon compared with rat neutrophils suggests the presence of a different prostacyclin receptor located on enteric neurones.
Wise
H
H
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
Qian
Y M
YM
Jones
R L
RL
D000085:Acetates / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003511:Cyclohexanols / Q000494:pharmacology; D004347:Drug Interactions; D011464:Epoprostenol / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D009504:Neutrophils / Q000187:drug effects / Q000648:ultrastructure*; D010080:Oxazoles / Q000494:pharmacology; D010642:Phenoxyacetates / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000187:drug effects*; D013268:Stimulation, Chemical
D000085:Acetates; D001643:Bridged Bicyclo Compounds; D003511:Cyclohexanols; C096584:EP 185; D010080:Oxazoles; D010642:Phenoxyacetates; D010975:Platelet Aggregation Inhibitors; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; C080116:BMY 42393; C084677:BMY 45778; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011464:Epoprostenol; C043867:cicaprost