Further evidence for multiple tachykinin receptors.

Rank order potency data for substance P (SP), physalaemin and eledoisin have been determined in a variety of assays in vitro. On the guinea-pig field stimulated vas deferens, physalaemin was approximately eight and five times more potent than eledoisin and SP respectively whereas in the rat field-stimulated vas deferens, eledoisin was approximately five times more potent than either physalaemin or SP. It would appear that the guinea-pig preparation has a preponderance of 'P'-receptor subtypes, whereas the rat preparation contains mainly 'E'-receptor subtypes. We have attempted to validate the hypothesis that there are multiple tachykinin receptors. Experiments have been performed with the guinea-pig urinary bladder in vitro, using phenoxybenzamine (20 microM, 30 min) to alkylate receptor sites and using excess eledoisin (0.2-0.4 microM, 30 min) to protect receptors selectively against the effects of this agent. Our results showed that after pretreatment with phenoxybenzamine, the responses to eledoisin were significantly attenuated. Moreover, in the presence of excess eledoisin it was found that phenoxybenzamine was unable to produce any significant reduction of the subsequent responses. This difference between the responses to eledoisin and to other agonists suggests the existence of at least two different receptor subtypes for the tachykinins.