Abstract
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.