6533b82cfe1ef96bd128f682

RESEARCH PRODUCT

Antagonist discrimination between subtypes of tachykinin receptors in the guinea-pig ileum.

subject

description

1. The effects of substance P and eledoisin on spontaneous and electrically-evoked release of [3H]acetylcholine, and on smooth muscle were studied in the guineapig myenteric plexus-longitudinal muscle preparation preloaded with [3H]choline. Substance P and eledoisin caused transient increases in spontaneous release of [3H]acetylcholine and in longitudinal muscle tone. Both tachykinins were equipotent in contracting the muscle, but eledoisin was more potent than substance P in eliciting [3H]acetylcholine release. The release caused by substance P was enhanced in the presence of naloxone and scopolamine which suggests that the release is modulated through opioid and muscarinic receptors. 2. Substance P and eledoisin inhibited the release of [3H]acetylcholine evoked by electrical stimulation at 0.1 Hz. The inhibition was not due to an activation of α-adrenoceptors, histamine or opioid receptors. The substance P antagonists (d-Pro2, d-Trp7,9)SP (10 and 30 μM) and (Arg5, d-Trp7,9, Nle11)SP5–11 (1 and 10 μM) competitively antagonized both the contractile effects of substance P and eledoisin, and the inhibition by the tachykinins of the electrically-evoked release of [3H]acetylcholine. The increase in spontaneous [3H]acetylcholine release elicited by substance P and eledoisin was not prevented by the substance P antagonists. 3. The results suggest that the neuronal receptor whose activation causes inhibition of acetylcholine release and the smooth muscle receptor correspond to the SP-P type, whereas the neuronal receptor mediating an increase in spontaneous acetylcholine release is of the SP-E type. The two antagonists, (d-Pro2, d-Trp7,9)SP and (Arg5, d-Trp7,9, Nle11)SP5–11, selectively block only the SP-P receptor.