PTX-SENSITIVE G-PROTEINS AND PERMISSIVE ACTION OF PROSTACYCLIN IN NEWBORN PIG CEREBRAL-CIRCULATION

The present study of newborn pig cerebral circulation investigated the role of pertussis toxin (PTX)-sensitive GTP binding proteins in the p ermissive action of prostacyclin in specific dilator responses. Pial a rterioles of anesthetized piglets were observed through closed cranial windows. The piglets were treated topically with PTX and intravenousl y with indomethacin. The effects of hypercapnia (10% CO2 ventilation) and topical 5,6-epoxyeicosatrienoic acid (5,6-EET) on pial arteriolar diameter were noted before and after the intervention. Samples of the artificial cerebrospinal fluid (aCSF) were collected from beneath the cranial windows for determination of the cAMP concentration. After adm inistration of PTX, indomethacin still abolished pial arteriolar dilat ion to both hypercapnia and 5,6-EET and also inhibited the cAMP elevat ion caused by hypercapnia. The addition of phorbol 12-myristate 13-ace tate (PMA), but not iloprost, restored the increase in cAMP and vascul ar responses to hypercapnia and 5,6-EET. Therefore, in the newborn pig cerebral microvasculature, PTX appears to inhibit a G protein involve d in the permissive action of prostacyclin. However, the protein kinas e C (PKC) activator PMA appears to act downstream from the block, and, therefore, the permissive action of PMA is not affected by PTX. We su ggest that the prostacyclin IP receptor may be coupled to phospholipas e C via a PTX-sensitive G protein that normally permits vasodilation t o specific stimuli via activation of a PKC, resulting in phosphorylati on of a component of the adenylyl cyclase pathway.