Guanine nucleotides decrease the affinity of substance P binding to its receptor.
The inhibitory effect of guanine nucleotides on the binding of 125I-Bolton-Hunter conjugated substance P (125I-BHSP) to rat submaxillary gland membranes has been confirmed and further explored. The evidence presented here indicates that this is due to a marked loss of binding affinity. In the presence of 5'-guanylyl imidodiphosphate (GppNHp) there is (1) a greater than or equal to 20-fold increase in the Kd as determined by Scatchard analysis and (2) the concentration of SP required to inhibit half of the 125I-BHSP binding (IC50) increased approximately 30-fold. Consistent with a marked decrease in affinity is an approximately 100-fold increase in the rate of dissociation of 125I-BHSP following addition of GppNHp. Complete restoration of high-affinity binding was achieved by removal of the guanine nucleotide.
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
J
J
Luber-Narod
N D
ND
Boyd
S E
SE
Leeman
D006150:Guanine Nucleotides / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D013388:Succinimides
C043194:Bolton Hunter reagent-substance P conjugate; D006150:Guanine Nucleotides; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013388:Succinimides; D013373:Substance P; D006165:Guanylyl Imidodiphosphate