The substance P receptor subtype modulating catecholamine release from adrenal chromaffin cells

Area of Science:

• Neuroendocrinology
• Cellular Signaling
• Pharmacology

Background:

• Substance P (SP) exhibits dual roles in regulating catecholamine (CA) release from bovine adrenal chromaffin cells.
• SP inhibits acetylcholine (ACh)- or nicotine-evoked [3H]norepinephrine ([3H]NE) release.
• SP also confers protection against desensitization of these nicotinic responses.

Purpose of the Study:

• To identify the specific SP receptor subtypes involved in SP's modulatory effects on CA release.
• To characterize the pharmacological properties of SP receptors in adrenal chromaffin cells.

Main Methods:

• Utilized various SP-related tachykinins and synthetic analogues to probe SP receptor activity.
• Assessed the ability of these compounds to inhibit [3H]NE release and protect against desensitization.
• Compared the potency of different peptides in mediating SP's actions.

Main Results:

• Naturally occurring tachykinins (physalaemin, eledoisin, kassinin) were less potent than SP in both inhibiting release and protecting against desensitization.
• SP-methyl ester, an 'SP-P' receptor-selective analogue, acted as an agonist with potency similar to SP.
• [D-Pro2,D-Trp7,9]-SP, a known SP antagonist, functioned as a potent agonist in this system.
• The rank order of peptide potency for inhibition and protection was similar, suggesting a shared receptor mechanism.

Conclusions:

• Adrenal chromaffin cells possess SP receptors distinct from 'SP-P' and 'SP-E' subtypes.
• A novel SP receptor subtype mediates both the inhibitory and protective effects on catecholamine release.
• This newly identified receptor shares characteristics with SP receptors involved in histamine release from rat mast cells.