Use of substance P fragments to differentiate substance P receptors of different tissues.
The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000032:analysis* / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D018040:Receptors, Neurokinin-1; D012472:Salivation / Q000187:drug effects; D013116:Spinal Cord / Q000032:analysis*; D013373:Substance P / Q000494:pharmacology*
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018040:Receptors, Neurokinin-1; D013373:Substance P