Agonist and antagonist binding to tachykinin peptide NK-2 receptors.
The binding of tachykinin peptides and fragments to NK-2 receptor sites in hamster urinary bladder membranes was examined and compared to binding to NK-1 receptor sites in rat submandibular gland. Neurokinin A (NKA) and its C-terminal fragments bound with highest NK-2 affinity and selectivity. N-terminal fragments of NKA did not bind to either type of receptor. Kassinin and eledoisin were NK-2 selective while physalaemin, phyllomedusin, and uperolein were NK-1 selective. Of fifteen tachykinin antagonists examined, none exhibited appreciable affinity or selectivity (relative to agonists) for NK-1, NK-2, or rat cerebral cortical NK-3 receptor sites. NKA binding to NK-2 sites was stimulated by Mn++ greater than Mg++ greater than Ca++. At the optimal concentration, the Mn++ stimulation was due to both an increased Bmax and increased affinity. The nonhydrolyzable guanine nucleotide, GppNHp, reduced agonist binding but not antagonist binding to NK-2 receptor sites. The nucleotide effect was due to a reduction in both Bmax and affinity and was potentiated by Mn++. The results indicate that tachykinin NK-2 receptor sites possess distinct structural requirements for agonists and are linked to a G-protein coupling system.
Buck
S H
SH
Merrell Dow Research Institute, Cincinnati, OH 45215.
Shatzer
S A
SA
D000818:Animals; D001667:Binding, Competitive; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013329:Structure-Activity Relationship; D015320:Tachykinins; D001743:Urinary Bladder / Q000378:metabolism
D002413:Cations, Divalent; D009479:Neuropeptides; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D006165:Guanylyl Imidodiphosphate; D008345:Manganese