Desensitization to substance P-induced vasodilation in vitro is not shared by endogenous tachykinin neurokinin A.
Two mammalian tachykinins, substance P (SP) and neurokinin A (NKA), were measured by radioimmunoassay in canine cephalic blood vessels and tested for their vasoactivity in vitro. Levels of immunoreactive SP were approximately 2-3 times greater than those of immunoreactive NKA in common carotid, basilar, and middle cerebral arteries. Both endogenous tachykinins relaxed precontracted segments of common carotid and basilar arteries in a dose-dependent manner with an EC50 of 8.9 X 10(-11) M and 7 X 10(-10) M, respectively, when added cumulatively. Relaxation was endothelial dependent for both substances and not blocked or enhanced by pretreatment with indomethacin, propranolol, lithium chloride, or atropine. Neither SP nor NKA released 3H-inositol phosphates from phospholipid membranes of canine carotid segments after preincubation with 3H-inositol. SP but not NKA or the C-terminal fragments SP(4-11) caused desensitization to subsequent additions of itself but not to the relaxation induced by sodium nitroprusside, calcitonin gene-related peptide, or bradykinin. These studies demonstrate that at least 2 peptides derived from beta-preprotachykinin are contained within cephalic blood vessels and that these products share similar vasoactive properties but differ in their ability to desensitize vascular tachykinin receptors.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D015288:Neurokinin A; D009479:Neuropeptides / Q000032:analysis / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011863:Radioimmunoassay; D013373:Substance P / Q000032:analysis / Q000502:physiology*; D015320:Tachykinins; D014664:Vasodilation / Q000187:drug effects
D002712:Chlorides; D009479:Neuropeptides; D015320:Tachykinins; D013373:Substance P; D007294:Inositol; D001285:Atropine; D015288:Neurokinin A; D008094:Lithium; D011433:Propranolol; D018021:Lithium Chloride; D007213:Indomethacin