The tachykinin peptide family certainly represents one of the largest peptide families described in the animal organism. So far, more than 40 tachykinins have been isolated from invertebrate (insects, worms, and molluscs), protochordate, and vertebrate (skin, gastrointestinal tract, peripheral and central nervous system) tissues. Substance P (SP), first identified by bioassay as early as 1931 but sequenced only in 1971, several years after the elucidation of the structure of eledoisin from molluscan tissues and of physalaemin from amphibian skin, may be considered as a prototype of the tachykinins. Hitherto, as many as 19 tachykinins have been isolated from amphibian integument, and eight additional peptides have been isolated from amphibian gut and brain. Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B. Three main receptor subtypes for the tachykinins have been identified (NK1, NK2, and NK3), but their number is probably destined to increase. It is obvious that the peripheral and central effects of the tachykinins may substantially vary depending on the activation of different receptor subtypes. Matters are further complicated by the frequent capacity of the single tachykinins to bind, although with different affinity, to more receptors. It has been recognized that tachykinins have a variety of effects in physiological and pathological conditions, and there is evidence suggesting intrinsic neuroprotective and neurodegenerative properties of these neuropeptides. This review provides an update on the current body of knowledge regarding tachykinin occurrence and distribution in the animal kingdom, from the lowest invertebrates to man, and the physiological and pharmacological actions of tachykinins outlining the pregnant importance of this large peptide family.

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Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus PhyUomedusa, that have a higher affinity and selectivity for 6 opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of PhyUomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, deltorphins I and II, show an even higher affinity for 6 receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phylomedusa skin, dermorphin, which is highly selective for ,u-opioid receptors. These peptides all have the N-terminal sequence Tyr-D-Xaa-Phe, where D-Xaa is either D-alanine or D-methionine. While this structure seems to be capable of activating both pA and 6 opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.The endogenous opioid ligands isolated from vertebrate brain show little selectivity toward the different types of opioid receptors. Peptides isolated from amphibian skin appear to be more selective. In 1981 Montecucchi et al. (1) extracted from the skin of the Argentinian frog Phyllomedusa sauvagei a heptapeptide named dermorphin, which preferentially binds to A-type opioid receptors (2). By recombinant DNA techniques, it was demonstrated that dermorphin, like numerous other peptides, is derived in multiple copies from larger precursors. In addition, from inspection of the sequence of one of the cloned cDNAs for these precursors, the existence of another heptapeptide with an N-terminal region similar to that of dermorphin was predicted (3). We recently succeeded in isolating small quantities of this peptide from the skin ofP. sauvagei and named it deltorphin, because of its high affinity and selectivity for the 8 opioid binding site (4). Both dermorphin and deltorphin contain a D amino acid (D-alanine and D-methionine, respectively) as the second amino acid. In the cloned cDNAs, codons for the corresponding L amino acids-i.e., GCG for alanine and ATG for methionine-were found at these positions. This characteristic suggested that the processing of these peptides includes a reaction whereby an L amino acid residue is converted to its D isomer within peptide linkage (3). Here we describe the isolation of two other heptapeptides from the skin of Phyllomedusa bicolor, which show an affinity and selectivity for 8 opioid receptors several times higher than that of deltorphin and the cyclic enkephalin derivative enkephalin (DPDPE, where D-Pen is D-penicillamine) (5). Once again, these peptides contain a D-alanine residue in the second position and share with dermorphin and deltorphin the N-terminal sequence Tyr-D-Xaa-Phe. We refer to these peptides, which differ by the presence of an aspartic or glutamic residue in position 4,...

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