ABSTRACT
alpha-Bungarotoxin (alpha Bgt) was shown to inhibit the binding of the 125I-labeled substance P (SP) and eledoisin (EL) to the rat brain membranes with Kl values of 8.0 +/- 5.0 x 10(-8) and 1.1 +/- 0.5 x 10(-6) M, respectively. Lower inhibitory activity was manifested by several other postsynaptically acting snake venom neurotoxins. The alpha Bgt inhibition of SP binding with a Kl value of 8.5 +/- 5.5 x 10(-8) M to solubilized preparations of the rat brain membranes was demonstrated. The capacity to displace SP was found for d-tubocurarine and phencyclidine, although at concentrations considerably higher than those affecting the nicotinic acetylcholine receptors (AChRs). The results obtained suggest that some of the alpha Bgt-binding polypeptides, distinct from neuronal AChRs, may be functionally associated with the tachykinin receptors (TchR).
Subject(s)
Brain/metabolism , Bungarotoxins/pharmacology , Receptors, Neurotransmitter/metabolism , Animals , Binding Sites/drug effects , Eledoisin/metabolism , Rats , Receptors, Tachykinin , Solubility , Substance P/metabolismABSTRACT
alpha-Bungarotoxin was found to inhibit effectively the binding of 125I-labelled substance P and eledoisin to membrane and to solubilize preparations of the rat brain. Other postsynaptic neurotoxins exerted similar but less pronounced influence on the interaction of tachykinins with their receptors. The obtained results suggest that some alpha-bungarotoxin-binding polypeptides in brain are components of tachykinin receptors.
Subject(s)
Brain/metabolism , Bungarotoxins/metabolism , Receptors, Neurotransmitter/metabolism , Tachykinins/metabolism , Amino Acid Sequence , Animals , Eledoisin/antagonists & inhibitors , Eledoisin/metabolism , Humans , Molecular Sequence Data , Rats , Receptors, Cholinergic/metabolism , Receptors, Tachykinin , Substance P/antagonists & inhibitors , Substance P/metabolism , TorpedoSubject(s)
Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives , Brain/metabolism , Receptors, Neurotransmitter/metabolism , Tachykinins/metabolism , Acetylmuramyl-Alanyl-Isoglutamine/metabolism , Animals , Binding, Competitive , Bungarotoxins/pharmacology , Chromatography, High Pressure Liquid , Rats , Receptors, Tachykinin , Substance P/antagonists & inhibitorsSubject(s)
Peptide Fragments/pharmacology , Substance P/pharmacology , Animals , Brain/drug effects , Brain/metabolism , Female , Guinea Pigs , Ileum/drug effects , Ileum/metabolism , In Vitro Techniques , Peptide Fragments/metabolism , Rats , Structure-Activity Relationship , Substance P/metabolism , Uterus/drug effects , Uterus/metabolismABSTRACT
Inhibition of binding of a substance P radioactive derivative with rat brain membranes by cyclic analogues of substance P was studied. The most active cyclic analogue had the inhibition constant 3 mM.
