Relative potencies of neurokinins in guinea pig trachea and human bronchus

The three endogenous neurokinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as NKA-(4-10), carbachol, acetylcholine and histamine, were tested in guinea pig tracheae and human bronchi in order to compare the activities of peptides and non-peptide agents and to characterize the neurokinin receptors by means of agonists. Neurokinin A and NKA-(4-10) were potent stimulants of the two preparations: pD2 values for NKA-(4-10) averaged 8.62 in the guinea pig trachea and 7.50 in the human bronchus. The rank order of potency of neurokinins was NKA-(4-10) greater than NKA greater than SP greater than NKB in the human bronchus and NKA-(4-10) greater than NKA greater than NKB greater than SP in the guinea pig trachea. SP was 2-3 orders of magnitude less active than NKA and appears to be a partial agonist. NKB is inactive on the human bronchus. Compared to non-peptide agents, NKA had an affinity 2-3 orders of magnitude greater than acetylcholine and histamine but produced only 75-80% of the maximal effect of acetylcholine. The present results indicate that neurokinins contract the human bronchus by activating a NK-A receptor type which is more sensitive to NKA than to SP and is insensitive to NKB. The guinea pig trachea appears to be a complex preparation containing not only NK-A but also other neurokinin receptors.