Substance P, neurokinin A and neurokinin B in the ocular response to injury in the rabbit.

1. Substance P (SP) and neurokinin A- (NKA)/neurokinin B (NKB)-like immunoreactivity (LI) were measured by radioimmunoassay in extracts of the rabbit uvea. The iris-ciliary body complex contained 3-4 times more NKA/NKB-LI than SP-LI. Tachykinins are thought to mediate many of the responses to ocular injury in the rabbit. Their possible role in the miosis and breakdown of the blood-aqueous barrier (BAB) was studied in vitro and in vivo. 2. In vitro, NKA had a more short-lasting contractile effect on the sphincter pupillae muscle than either SP or NKB, but SP was more potent than the other two. The tachykinin antagonist, spantide, dose-dependently suppressed the response to electrical stimulation (by 90% at 10(-4) M) and to the three tachykinins. An antiserum against SP (no cross-reaction with NKA or NKB) greatly suppressed the response to SP (by 90%) as well as to electrical field stimulation (by 40%). The responses to NKA and NKB were unaffected. 3. In vivo studies revealed that SP was more potent than NKA and NKB as a miotic. SP evoked a moderate breakdown of the BAB at high doses while NKA and NKB were virtually inactive. 4. We conclude that besides SP other tachykinins might play a role in the mediation of miosis in the rabbit eye but, of the three peptides investigated, only SP can be of importance for the breakdown of the BAB.