Intravenous infusions of the undecapeptide substance P caused a moderate but transient secretory response from the rat submandibular gland. The electrolyte composition of the saliva elicited by this peptide was qualitatively similar to that of the secretion induced by parasympathomimetic agents. Substance P inhibited the secretory response to acetylcholine and isoproterenol, but did not modify the binding of specific ligands to glandular autonomic receptors. It is concluded that this naturally occurring peptide plays a role in the physiologic regulation of salivary secretions, which involves both direct stimulatory effects and a modulating action on the effect of autonomic neurotransmitters on the salivary gland cells. The latter may involve similar effects of substance Pand the neurotransmitters on a metabolic pathway localized beyond receptor activation.
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