Substance P: Its Pharmacology and Physiological Roles

Abstract

Summary. The recent identification and synthesis of the endecapeptide substance P has renewed interest in this naturally occurring compound. The original substance P of Euler and Gadduni was a mixture of biologically active substances, some of which were peptides. The peptide component was responsible for gut-contracting, hypotensive and sialogogic properties attributed to substance P. For almost 40 years following its discovery, substance P resisted isolation and purification. Even the most highly active preparations were heterogeneous and there was a divergence of results from experiments using preparations which were partially purified by different techniques. Nevertheless, much of the early work on the distribution and pharmacology of crude substance P has been confirmed using the synthetic endecapeptide and has stimulated research towards the elucidation of a possible functional role for substance P. Most proposed functions have been highly speculative but, at present, evidence is accumulating in support of a physiological role for substance P as a neurotransniitter in sensory pathways. DISCOVERY, PURIFICATION AND ISOLATION OF SUBSTANCE P.While investigating the distribution of acetylcholine in various tissues in 1931, Euler and Caddum detected the presence of a substance in alcoholic extracts of equine brain and intestine which stimulated contraction of isolated rabbit intestine. On intravenous administration to anaesthetized rabbits, this preparation briefly lowered the blood pressure. These effects differed qualitatively from those of acetylcholine and, in addition, were not inhibited by atropine. The active moiety found in the dried extracts was given the working designation "preparation P" and was shown to differ in its chemical and biological properties from other smooth muscle stimulating substances then known, viz. histamine and the adenine nucleotides. The new active factor, provisionally named substance P (Caddum and Schild, 1934), was first recognised as a protein-like material by Euler (1936a).

Distribution of substance P‐like immunoreactive nerve fibers in temporomandibular joint soft tissues of monkey

“…The polypeptide substance P was first visualized with immunohistochemistry by HoKFELT et al (11) and has been suggested to be ao excitatory transmitter in certain primary sensory neurons (11)(12)(13) and it has been postulated that substance P is involved in pain transmission (13)(14)(15)(16). Substance P is present in the GNS (17) and in most peripheral tissties (18). LEVINE (19) demonstrated the presence of substance P in the knee joints of rat by a radioimmunoassay technique.…”

Enzyme‐Linked Immunosorbent Assay of Substance P: A Study in the Eye

“…Substance P (SP), an undecapeptide, has been shown to be widely distributed in many mammalian species (Bury and Mashford, 1977). The peptide has also been detected in the eye, both in the uvea and in the retina (see Stjernschantz, 1981).…”

Circular Dichroism Studies of Substance P and Its C‐terminal Sequences

“…ProGlnGln-Phe-PheCly-Leu-MetNH, S P 8 Lys-ProClnGln-Phe-PheCly-Leu-MetNH, SP 9 Pro-Lys-ProClnGln-Phe-PheGly-Leu-MetNH, SP 10 Arg-Pro-Lys-ProGln-Gln-Phe-PheGly-Leu-Met NH, SP 1 1 PheNH, M 1 Phe-PheNH, M 2 Gln-Phe-PheOMe M 3 IleGly-Leu-MetNH, EL 4 action on the smooth muscle (Bergmann er al., 1974(Bergmann er al., ,1975Bury & Mashford, 1977). It has been shown that C-terminal sequences of substance P gain a maximum of activity at the octa/nonapeptide.…”