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Guanine nucleotides regulate [3H]substance P binding in rat small intestine
Authors:K E Smith  W P Hoss
Institution:Center for Brain Research, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, U.S.A.
Abstract:The binding of 3H]substance P (SP) to membranes of the rat small intestine demonstrates specific binding to receptors having more than one affinity for SP. The values of the binding parameters for the high-affinity site obtained from a non-linear regression analysis are as follows: KD = 0.25 nM, Bmax = 149.5 fmol/mg protein. Inhibition curves of 3H-SP binding using various unlabeled tachykinins show that the high-affinity receptor is of the P-subtype, having the highest affinity for SP and lower affinities for eledoisin and kassinin. Guanine nucleotides and sodium independently reduce the binding of 3H-SP to the high-affinity receptor in a dose-related manner; GTP and GDP are more potent than GMP. The reduction of specific SP binding by GTP can be ascribed primarily to an increase in the off-rate. The effects of guanine nucleotides on 3H-SP binding to membranes of rat small intestine suggest that the high-affinity receptor is linked to an effector by a GTP-binding regulatory protein.
Keywords:substance P receptors  tachykinin receptors  enteric nervous system  small intestine  guanine nucleotide  GTP
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