Receptor-mediated Ca++ entry in blood vessels.
The importance of receptor-mediated Ca++ entry (RMCa++E) relative to Ca++ release and potential-dependent Ca++ entry (PDCa++E) in agonist-induced responses in rabbit aorta and renal artery was quantitatively delineated by utilizing a solution without added Ca++ containing low ethyleneglycol bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) plus D600 to inhibit PDCa++E. Adding an approximate ED80 concentration of norepinephrine (NE; 3 x 10(-7) M), histamine (Hist; 3 x 10(-6) M), or serotonin (5HT; 3 x 10(-6) M) to this solution results in a transient increase in developed force that is attributed to release of a limited cellular pool of Ca++. (NE greater than Hist much greater than 5HT). When the concentrations are approximately equipotent (NE, 3 x 10(-7) M; Hist, 3 x 10(-5) M; 5HT, 10(-5) M) the Ca++ release component increases for Hist and 5HT such that NE = Hist greater than 5HT. Subsequent addition of Ca++ results in an increase in developed force that is sustained and represents RMCa++E. In aorta, RMCa++E can account for 91% of the total NE-induced developed force; for an equipotent concentration of Hist, 71%; and for an equipotent concentration of 5HT, only 37%. This capacity for stimulating RMCa++E is inversely related to the sensitivity of these agonists to the PDCa++E blocker, D600 (5HT much greater than Hist greater than NE). Chronic Mg++ potentiates control responses to NE in normal Ca++, but depresses the sensitivity to Ca++ in the RMCa++E concentration response relationship. The sustained response associated with RMCa++E is only minimally relaxed or inhibited by Mg++ (acute) and is completely inhibited or slowly and completely relaxed by La . In renal artery, a similar approximate ED80 concentration of NE (3 x 10(-6) M) results in a NE-induced transient response attributed to Ca++ release that is 60% less than that seen in aorta, whereas the RMCa++E component in renal artery accounts for 78% of the total response (only 10% less than in aorta). Thus, it appears that there are pharmacologically distinct Ca++ channels in some blood vessels that are differentially activated in a selective and potential-independent manner as a result of specific agonist-receptor interactions.
Hester
R K
RK
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University, College Station 77843.
D000818:Animals; D001013:Aorta, Thoracic; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008274:Magnesium / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D012077:Renal Artery; D012701:Serotonin / Q000494:pharmacology
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D011956:Receptors, Cell Surface; D012701:Serotonin; D006632:Histamine; D008274:Magnesium; D009638:Norepinephrine