Peptide transmitters of primary sensory neurons: similar actions of tachykinins and bombesin-like peptides.

Previous studies have demonstrated that two peptides, substance P (SP) and substance K (SK), are contained in a common prohormone--beta-preprotachykinin. Both peptides are cleaved from the prohormone and appear to coexist throughout the brain. This study evaluated the behavioral activity of SK and compared it to the activities of SP, bombesin (BN), and structurally related peptides. After intraspinal injection, all of the peptides induced "bite/scratch" behaviors, which differed in durations of action. The specific rank order of these durations of action were: BN greater than gastrin releasing peptide (GRP) = ranatensin (RT) greater than neuromedin B (NMB) greater than kassinin (KASS) = SK = SP and ranged from dose-dependent maxima of approximately 2 min (SP) to approximately 100 min (BN). To examine the possibility that differences in durations of action are due to differences in rates of proteolytic degradation, each peptide was incubated in spinal cord homogenates at 37 degrees C, and the degradation rates were monitored by radioimmunoassay (RIA) and by bioassay. The lengths of incubation time required to produce approximately 90% degradation of peptide immunoreactivity varied across peptides from less than 5 min (SP) to more than 60 min (BN and RT). Degradation of bioactivity generally paralleled degradation of immunoreactivity. The results of this study suggest that durations of nociceptive effects produced by the peptides tested are due, in part, to their resistance to proteolytic degradation.