B1 and B2 kinin receptors on cultured rabbit superior mesenteric artery smooth muscle cells: receptor-specific stimulation of inositol phosphate formation and arachidonic acid release by des-Arg9-bradykinin and bradykinin.
In this study we investigated receptor-specific cellular signals elicited by kinin agonists in cultured rabbit superior mesenteric artery smooth muscle cells. Kinins promoted an increase in inositol phosphate formation and arachidonic acid release in these cells. The responses elicited by des-Arg9-bradykinin (des-Arg9-BK), a B1 kinin agonist, were antagonized by des-Arg9[Leu8]-BK, a B1 kinin antagonist, but not by D-Arg0[Hyp3,D-Phe7]-BK, a B2 kinin antagonist. In contrast, the responses elicited by BK, a B2 kinin agonist, were antagonized with the opposite antagonist specificity. Lys-BK or kallidin displayed a biphasic concentration-response relationship and each response phase was selectively antagonized by each of the above antagonists. Des-Arg9-BK, at 1 microM, promoted a sustained increase primarily in the level of inositol monophosphate which was partially dependent on extracellular Ca++, whereas 1 microM BK promoted a transient increase in the levels of inositol trisphosphate, inositol bisphosphate and inositol monophosphate, and the formation of inositol monophosphate was only marginally dependent on extracellular Ca++. Pretreatment with 0.1 microM phorbol 12-myristate-13-acetate resulted in inhibition of both des-Arg9-BK- and BK-promoted inositol phosphate formation. ADP-ribosylation by pertussis toxin (100 ng/ml) had no effect on the inositol phosphate response elicited by either of these agonists. The major finding in this study is that pharmacologically typical B1 and B2 kinin receptors are both coupled to inositol phospholipid metabolism and arachidonic acid release. These cells should provide an excellent system for further studies of the function and regulation of B1 and B2 kinin receptors.
Tropea
M M
MM
Department of Biochemistry, University of Texas Health Science Center, San Antonio.
Gummelt
D
D
Herzig
M S
MS
Leeb-Lundberg
L M
LM
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000502:physiology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007609:Kallidin / Q000494:pharmacology; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000187:drug effects / Q000502:physiology*
D007295:Inositol Phosphates; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C024626:bradykinin, des-Arg(9)-; D016718:Arachidonic Acid; D007609:Kallidin; D019204:GTP-Binding Proteins; D001920:Bradykinin