Vasoconstriction in rat isolated mesentery and small intestine in response to various activators of protein kinase C.
The vasculature of rat isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution (GPSS). When 5-hydroxytryptamine (5HT, 1 x 10(-4) M), or the calcium ionophore A23187 (1 x 10(-4) M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1 x 10(-6) M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1 x 10(-6) M) or thymeleatoxin (TMX, 1 x 10(-6) M) was added to the GPSS for 5 min there was a gradual rise in perfusion pressure, whereas resiniferatoxin (RFX, 1 x 10(-6) M) was without effect. Pre-treatment of the tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced the rise in perfusion pressure in response to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187. Platelet-activating factor (PAF, 5 x 10(-6) M) caused an almost immediate but transient rise in perfusion pressure, followed by a more gradual rise, neither response being blocked by Ro 31-8220. When blood vessels of the mesentery alone were perfused with gelatin-free PSS, PAF caused a transient rise in perfusion pressure, but with no subsequent gradual rise over 5 min. After Ca(2+)-depletion this transient response was also absent. In contrast, when blood vessels were perfused with gelatin-free PSS, DOPPA and TMX still caused gradual rises in perfusion pressure, which were totally abolished by Ro 31-8220. TMX had no effect at all when the tissue was depleted of Ca2+, whereas the response to DOPPA was only partially reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Northover
A M
AM
Department of Pharmacy, School of Applied Sciences, De Montfort University, Leicester, UK.
Northover
B J
BJ
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007421:Intestine, Small / Q000098:blood supply*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008643:Mesentery / Q000098:blood supply*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D007211:Indoles; D007527:Isoenzymes; D010703:Phorbol Esters; D010656:Phenylephrine; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D012701:Serotonin; D000001:Calcimycin; C029704:12-deoxyphorbolphenylacetate; C080287:thymeleatoxin; D011493:Protein Kinase C; D002118:Calcium; C064758:Ro 31-8220