In the eye (D‐Pro2, D‐Trp7,9)‐SP is a substance P agonist, which modifies the responses to substance P, prostaglandin E1 and antidromic trigeminal nerve stimulation

Abstract

A substance P analogue, (D-Pro², D-Trp^7,9)-SP, has been described to have SP antagonistic and SP agonistic effects in different tissues. We have investigated the effects of (D-Pro², D-Trp^7,9)-SP on the sphincter pupillae muscle, the blood aqueous barrier (BAB) and the intraocular pressure (IOP) in the albino rabbit eye. We also investigated the modifying effects of (D-Pro², D-Trp^7,9)-SP on miosis, BAB damage and IOP rise caused by SP, prostaglandin E₁ (PGE₁), capsaicin and on the miosis caused by electrical intracranial antidromic trigeminal nerve stimulation (NV stim). Endogenous PG synthesis was inhibited by systemic indomethacin i. v., cholinergic influence on the pupil size was inhibited with biperiden, i. v., adrenergic nerve influence by cervical sympathectomy just prior to the expts. Tubocurarine chloride was used to cause relaxation of striated muscles in the expts with NV stim. We found 100 μg (D-Pro², D-Trp^7,9)-SP to cause miosis, breakdown of the BAB with heavy leakage of Evans blue into the ciliary processes and aqueous humor, and a rise in IOP. At 10 μg (D-Pro², D-Trp^7,9)-SP caused slight miosis and did not inhibit the miosis caused by SP or capsaicin, but caused a significant reduction of the miotic response caused by PGE₁ and NV stim. The rise in protein concentration in the aqueous humor caused by SP or PGE₁ was slightly but significantly lower after pretreatment with (D-Pro², D-Trp^7,9)-SP. Thus (D-Pro², D-Trp^7,9)-SP was found to act as a SP agonist on the sphincter pupillae muscle, on the BAB and IOP. However, (D-Pro², D-Trp^7,9)-SP seemed to have some SP antagonistic effects on mechanisms that require sensory nerve conduction e. g. miosis caused by PGE₁ and NV stim. The antagonistic mechanism is not clear. The SP analogue may have an unspecific membrane stabilizing effect or a toxic effect or block SP receptors on the sensory nerve fibers. Such effects of (D-Pro², D-Trp^7,9)-SP may explain also why the rise in protein concentration in the aqueous humor caused by SP and PGE₁ was lower in eyes pretreated with (D-Pro², D-Trp^7,9)-SP.