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V Erspamer

Publications and source records attributed to V Erspamer.

At least 19 recordsLinked to original sources
PubMed1992

Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat.

Three naturally occurring dermorphin-like peptides from the skin of the frog Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted analogs were synthesized, their binding profiles to opioid receptors were determined, and their biological activities were studied in isolated organ preparations and intact animals. The opioid binding profile revealed a very high selectivity of these peptides for mu sites and suggested the existence of two receptor subtypes, of high and low affinity. The peptides tested acted as potent mu opioid agonists on isolated organ preparations. They were several times more active in inhibiting electrically evoked contractions in guinea pig ileum than in mouse vas deferens. When injected into the lateral brain ventricle or peritoneum of rats, the high-affinity-site-preferring ligand, [Lys7-NH2]dermorphin, behaved as a potent analgesic agent. By contrast, the low-affinity-site-preferring ligand, [Trp4,Asn7-NH2]dermorphin, produced a weak antinociception but an intense catalepsy.

Amino Acid Sequence↗
PubMed1992

Long-term sensitization to the activation of cerebral delta-opioid receptors by the deltorphin Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 in rats exposed to morphine.

In experiments to evaluate responses to the activation of cerebral delta-opioid receptors, repeated daily injection of the selective delta-opioid agonist Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 ([D-Ala2]deltorphin II) into rat brain resulted in the development of tolerance, whereas repeated daily injection or continuous infusion of morphine resulted in sensitization to the behavioral activating effects of the delta-opioid agonist. Although the rats did not modify their spontaneous locomotor activity after morphine withdrawal, they became markedly hyperresponsive to the locomotor and stereotypy-producing effects of a challenge dose of the delta-opioid agonist. Sensitization to activation of delta-opioid receptors persisted for at least 60 days after discontinuing morphine treatment. These results show that the development of tolerance and long-term sensitization to opioids involves delta-opioid as well as mu-opioid receptors.

Animals↗
PubMed1991

Structure-activity relationships of the delta-opioid-selective agonists, deltorphins.

Deltorphins are naturally occurring peptides with high affinity and selectivity for delta-opioid receptors. They share with dermorphin, another mu-selective opioid agonist, the same N-terminal tripeptide Tyr-D-Xaa-Phe, where D-Xaa is a D-Ala or a D-Met residue. This common sequence appears to be essential for the best fitting of the peptides to both mu- or delta-opioid sites. We studied the changes in receptor affinity and selectivity and in biological potency of deltorphins due to shortening of the sequence, C-terminal deamidation or single amino acid substitutions. The results support the view that a code addressing the molecule towards delta-opioid sites is expressed in the C-terminal region of these peptides. This addressing domain confers high delta-selectivity to the ligand in the following two ways: (i) increased affinity for delta-sites; (ii) decreased affinity for mu-sites. The sequence of the C-terminal tripeptide appears to be responsible for the high delta-affinity of the molecules. Negatively charged side chains inhibit mu-binding and enhance delta-selectivity.

Amino Acid Sequence↗
PubMed1991

Different receptors mediate the action of bombesin-related peptides on gastric smooth muscle cells.

Recent studies suggest that different subtypes of receptors may mediate the action of various bombesin-related peptides in different tissues. In the present study the ability of bombesin and its structurally related peptides [litorin, gastrin-releasing peptide (GRP), GRP18-27, neuromedin B, [Leu8]litorin, and bombesin nonapeptide BN(6-14)] to interact with smooth muscle cells isolated from guinea pig stomach was investigated. Each peptide induced a specific contractile response with potencies (D50 in pM) of [Leu8]litorin (0.7) greater than bombesin (1.2) greater than litorin (3) greater than neuromedin B (3.5) = GRP (3.8) = GRP18-27 (3.9) greater than BN(6-14) (70.9). The specific bombesin receptor antagonist psi 13,14-bombesin differed in its potency for inhibiting equipotent concentrations of bombesin, GRP, or neuromedin B, was equipotent for bombesin or GRP (IC50 12.7 and 22.1 nM), and was 11 times less potent for neuromedin B (IC50 234.5 nM), suggesting the presence of subtypes of receptors mediating the action of bombesin-related peptides. To further investigate this possibility, a technique of receptor protection that enables selective preservation of one receptor type was used. GRP or bombesin protected completely the response to GRP or bombesin but abolished the subsequent contractile response to neuromedin B. Neuromedin B, instead, protected only the response to neuromedin B. These results demonstrate that gastric smooth muscle cells possess specific receptors that interact with bombesin-related peptides and that two receptor subtypes mediate the contractile response to these peptides: one subtype is selective for bombesin or GRP, the other for neuromedin B.

Amino Acid Sequence↗
PubMed1989

Facilitation of [3H]acetylcholine and [3H]5-hydroxytryptamine release from rat cerebral cortex synaptosomes by a factor extracted from the skin of the Australian frog Pseudophryne coriacea.

A partly purified extract of the skin of the Australian frog Pseudophryne coriacea (PsC) evoked the release of [3H]acetylcholine [( 3H]ACh) and of [3H]5-hydroxytryptamine [( 3H]5-HT) from superfused rat cerebral cortex synaptosomes prelabeled with [3H]choline or [3H]5-HT, respectively. The PsC-evoked release of both transmitters was sensitive to tetrodotoxin and was strictly Ca2+-dependent. The release of [3H]5-HT caused by PsC was unaffected by the 5-HT uptake inhibitor citalopram. Activation of muscarinic autoreceptors by ACh or of serotonin autoreceptors by 5-HT depressed the PsC-evoked release of [3H]ACh or of [3H]5-HT, respectively. It is concluded that PsC elicits a Ca2+-dependent exocytotic-like transmitter release, possibly by opening Na+ channels in the presynaptic membrane.

Acetylcholine↗
PubMed1989

Deltorphin, a novel amphibian skin peptide with high selectivity and affinity for delta opioid receptors.

With a cDNA library prepared from skin of Phyllomedusa sauvagei, the sequence of the precursor of dermorphin was elucidated recently. The sequence suggested the existence of another peptide, distantly related to dermorphin. Two variants of this peptide have now been synthesized containing either L- or D-methionine as the second amino acid. The peptide containing the D-methionine exhibited high-affinity and selectivity for delta opioid receptors in the mouse vas deferens and in rat brain homogenates. Moreover, using the synthetic peptide as marker, we could isolate small quantities of the corresponding natural peptide containing D-methionine as the second amino acid from skin extracts of Phyllomedusa sauvagei. The name deltorphin is proposed for this new peptide and its sequence is Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2.

Animals↗
PubMed1989

Pumiliotoxin B-like alkaloid in extracts of the skin of the Australian myobatrachid frog Pseudophryne coriacea: effects on the systemic blood pressure of experimental animals and the rat heart.

Semi-purified extracts of the skin of the Australian myobatrachid frog Pseudophryne coriacea (PS)displayed striking, reversible and, in part, dose-dependent effects on the systemic blood pressure of the rat and other experimental animals, as well as on the rat heart. The blood pressure response in the rat consisted typically in an abrupt, short-lasting fall, followed by a conspicuous, more persistent rise. The fall in pressure was abolished by atropine and potentiated by physostigmine, indicating a cholinergic mechanism; rise was abolished by prazosin and guanethidine, suggesting a release of catecholamines from adrenergic nerve terminals in the vasculature. Tachyphylaxis was the obvious result of exhaustion of stores of catecholamines. On the heart, as shown in the electrocardiographic tracings, PS produced a variety of rhythm disorders, attributable both to the release of aminergic transmitters and to a direct effect on the myocardium. Whereas the pressure and electrocardiographic responses were virtually unaffected by calcium channel antagonists and agonists, all the effects of PS were sharply reduced or completely abolished by the sodium channel blocker tetrodotoxin. This suggests that activation of sodium channels may play a role in the mechanism of action of PS. However, the exact nature of ionic flux(es)influenced by the extract of frog skin remains to be established.

Adrenalectomy↗
PubMed1989

Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta 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 Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affinity for delta receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phyllomedusa skin, dermorphin, which is highly selective for mu-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 mu and delta opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.

Amino Acid Sequence↗
PubMed1989

Brain-gut-skin peptides: an update overview.

The authors present an overview of the main amphibian peptide families mainly derived from the skin and mostly discovered by Erspamer and his associates. The studies of the peptides do not only promote the understanding of their chemical, metabolical and physiological features of those molecules in amphibians, but also contribute to progress in our knowledge of the corresponding mammalian counterparts. Particular reference is made on sauvagine, tachykinin, bombesin and dermorphin families, offering new data mostly from personal contributions to this field.

Amphibians↗
PubMed1988

Parallel bioassay of 27 bombesin-like peptides on 9 smooth muscle preparations. Structure-activity relationships and bombesin receptor subtypes.

Thirteen natural bombesin-like peptides and 14 synthetic analogues were submitted to parallel bioassay on 9 smooth muscle preparations in order to determine their relative potency, in comparison to bombesin and litorin. The natural peptides of the bombesin subfamily showed a uniformly high or moderate potency on all preparations. However, synthetic bombesins of shorter chain length (hepta- and octapeptides) manifested a good potency only on the rat uterus preparation. Among the peptides of the litorin and phyllolitorin subfamilies, only litorin and ranatensin presented a full spectrum of potency, equalling or even surpassing that of bombesin. All other natural and synthetic members of the two subfamilies showed a sharply dissociated spectrum of potency on the different smooth muscle preparations. The only exception was the rat urinary bladder and, in part, the chicken intestine, on which the peptides displayed a uniformly high potency, comparable to, or even greater than that of bombesin. The present results help to explain structure/activity relationships and suggest the probable existence, in the periphery, of multiple bombesin receptor subtypes.

Animals↗
PubMed1986

An immunoreactive peptide in milk contains bombesin-like bioactivity.

Parallel in vitro bioassays using rat uterus and guinea pig large intestine tissues specific for the bombesin family of peptides, demonstrated that the bombesin-like peptides present in bovine milk can produce a dose-related response similar to bombesin and litorin. The bioactivity of this type of milk peptide appeared to be approximately 20-50% as active as the amphibian peptides. These data support the proposal that a bombesin immunoreactive peptide in milk contains bombesin bioactivity.

Animals↗
PubMed1986

A potent factor in extracts of the skin of the Australian frog, Pseudophryne coriacea--III. Potentiation of contractions elicited in avian and mammalian isolated skeletal muscle preparations by direct and indirect electrical stimulation.

Extracts of the skin of the Australian frog Pseudophryne coriacea displayed a striking potentiating effect on contractions evoked in isolated skeletal muscle preparations of mammals (phrenic nerve diaphragm) and birds (chick biventer cervicis and semispinalis muscles) by indirect and direct electrical stimulation. There was both a conspicuous increase in the amplitude of the twitch, up to 10-fold, and a remarkable prolongation of the duration of the twitch. The effect was dose- and frequency-dependent. In the presence of the extract, fusion of twitches after tetanic stimulation occurred earlier. No tachyphylaxis upon repeated stimulation by the extract was observed and the response to large doses persisted, declining slowly, for hours. These effects must be ascribed to an alkaloid related in structure to pumiliotoxin B. Response to the extract of Pseudophryne coriacea by indirectly-stimulated preparations was potentiated by physostigmine and blocked by tubocurarine and alpha-bungarotoxin, demonstrating that in these preparations the extract acted pre-synaptically to facilitate the release of acetylcholine from motor nerve endings. However, the extract of Pseudophryne coriacea displayed equally potent effects in directly stimulated preparations, insensitive to physostigmine and to blockers of nicotinic acetylcholine receptors, indicating a direct action on the skeletal muscle. It is suggested that, like pumiliotoxin B, the Pseudophryne coriacea alkaloid may interfere in the regulation of calcium channels in both nerve and muscle fibres.

Acetylcholine↗
PubMed1986

Active peptides in the skins of two hundred and thirty American amphibian species.

Extracts prepared from dried or fresh skins of more than 200 American amphibian species were subjected to biological screening in order to determine occurrence and contents of peptides active on smooth muscle preparations, systemic blood pressure and, subordinately, external secretions, anterior pituitary and the central nervous system. The peptide families identified in skin extracts were as follows: caruleins (caerulein, phyllocaerulein), tachykinins (physalaemin, phyllomedusin), bombesins (phyllolitorin, [Leu8]phyllolitorin, rohdeilitorin), bradykinins (phyllokinin and others), sauvagine, dermorphins (dermorphin, [Hyp6]dermorphin), tryptophyllins (numerous peptides) and, finally, miscellaneous peptides. None of the above peptide families showed a widespread distribution, but all were restricted to particular amphibian genera or stocks. The hylid frogs of the Phyllomedusinae family occupy a unique position, as their skin displayed the greatest variety and abundance of active peptides ever found in any amphibian is destined to increase because numerous other peptide molecules await isolation, elucidation of structure and definition of possible biological activities.

Amphibian Proteins↗
PubMed1986

Indole-, imidazole- and phenyl-alkylamines in the skin of one hundred and forty American amphibian species other than bufonids.

Extracts prepared from dried or fresh skins of 140 American amphibian species, other than bufonids, were subjected to chemical and biological screening in order to determine the presence and concentrations of aromatic biogenic amines. The most frequent and abundantly occurring amine category was that of indolealkylamines, represented by their prototype 5-hydroxytryptamine and its N-methylated derivatives. Conjugated and cyclized indolealkylamines, typical for the toad skin, were apparently lacking. Phenylalkylamines were represented by two quaternary ammonium bases: leptodactyline and, very rarely, candicine. Leptodactyline was particularly abundant in leptodactylid frogs of the genus Leptodactylus. Histamine occurred in trace amounts in different species, in large amounts only in some Leptodactylus species of the "pachypus" section. On the other hand, N-methylated histamines and cyclized histamines (spinaceamines) were confined to the skin of Leptodactylus pentadactylus labyrinthicus. The possible taxonomical and evolutionary significance of amphibian skin amines is pointed out.

Amphibians↗