Postnatal changes in the substance P receptor on rabbit gastric smooth muscle.
We used radioligand binding to tissue homogenates and isometric contraction of muscle strips to characterize the substance P (SP) receptor on gastric smooth muscle from 1- (newborn) and 7-day-old and 4- and 11-wk-old (weanling) rabbits. Scatchard analysis for newborns was curvilinear, suggesting the presence of multiple binding sites. In newborns the dissociation constant (Kd) of high-affinity binding site was 2.2 +/- 0.3 nM, and the maximum binding (Bmax) was 0.57 +/- 0.06 pmol/mg DNA. The number of high-affinity binding sites decreased with age, disappearing by 11 wk. The Kd for the low-affinity site was more than two orders of magnitude greater than that of the high-affinity site. In competitive binding studies with [3H]SP, the order of potency for the neurokinins was SP much greater than neurokinin A (NKA) greater than neurokinin B (NKB), suggesting that the high-affinity binding sites were NK-1 receptors. [125I]NKA is also bound to newborn tissue homogenate with high affinity. With [125I]NKA the order was NKA greater than SP greater than NKB, suggesting that NK-2 receptors were also present. In contraction studies, atropine and tetrodotoxin had no effect on tachykinin-stimulated contraction, suggesting solely myogenic tachykinin effects on this tissue. In newborn rabbits, the potency and efficacy of SP and NKA were similar. The half-maximal effective dose (ED50) of SP was nearly two orders of magnitude less in newborn rabbits than in weanlings; the potency of NKA did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Hyman
P E
PE
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90502.
Kimura
S
S
Tomomasa
T
T
Yuan
Q X
QX
Snape
W J
WJ
McRoberts
J A
JA
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D015287:Neurokinin B / Q000494:pharmacology; D009994:Osmolar Concentration; D011817:Rabbits; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D013997:Time Factors
D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B