Comparison of the presence and actions of substance P and neurokinin A in guinea-pig taenia coli.

The presence and sites of action of two closely related tachykinins, substance P (SP) and neurokinin A (NKA), were examined in the taenia coli of the guinea-pig. SP- and NKA-like immunoreactivity (LI) were demonstrated histochemically in nerve fibres supplying the taenia. Chromatographic characterization of aqueous acetic acid extracts of taenia showed only one peak of SP-LI, corresponding in retention time to authentic SP, whereas there were multiple peaks of NKA-LI, the major one of which corresponded to authentic NKA. SP-LI and NKA-LI, determined by radioimmunoassay, were in a molar ratio of SP equivalents to NKA equivalents of 8.5:1 in taenia extracts. Extrinsic denervation of the caecum had no significant effect on the concentration of either SP-LI or NKA-LI or on their immunohistochemical distributions. Both SP and NKA (10(-10) to 10(-5) M) caused contractions of the taenia that were unaffected by hyoscine (10(-6) M), mepyramine (10(-6) M) or tetrodotoxin (5 x 10(-7) M), indicating that both peptides act directly on the smooth muscle of the taenia. Contractions to SP occurred after a short, but concentration-dependent, delay, reached a peak quickly, and then decayed. In contrast, NKA caused contractions after longer latencies, the peak was reached more slowly, and the response was maintained for up to 10 min. (D-Pro2, D-Trp7,9)-SP (10(-5) M) antagonised responses to SP and NKA to a similar degree. It is concluded that both NKA and SP should be considered as transmitter candidates for non-cholinergic nerve-mediated excitation in the taenia.