Prolactin releasing and luteinizing hormone inhibiting activity of dermorphin shorter homologues in the rat.
Dermorphin, a heptapeptide isolated from the skin of the frogs Phillomedusa sauvagei and Phillomedusa rhodei, is endowed with potent peripheral and central opioid-like activity. Intracerebroventricular (icv) injection of dermorphin (31.2, 62.5 and 125 pmol/100g) induced in ovariectomized (OVX) rats dose related rises and decreases in prolactin (PRL) and luteinizing hormone (LH) levels, respectively. The aim of this work was to evaluate the same endocrine responses after administration of shorter peptide amide homologues, related to the N-terminal sequence of dermorphin. These compounds retain a substantial analgesic activity although the latter decreases with the decrease in the number of amino acid residues. Icv administration of the hexapeptide homologue (dermorphin 1-6 amide) to OVX rats did not induce any PRL rise or LH inhibition, even at the high dose of 250 pmol/100g. The pentapeptide (dermorphin 1-5 amide), instead, increased PRL and decreased LH secretion, although the effect was significant only at the dose of 250 pmol/100g. Administration of the tetrapeptide (dermorphin 1-4 amide) induced a significant PRL rise and LH inhibition at both the doses of 125 and 250 pmol/100g. The tetrapeptide was the smallest fragment of the dermorphin moiety which caused endocrine responses while the tripeptide (dermorphin 1-3 amide) was completely ineffective in this context. These data indicate that a complete dissociation exists between the behavioral and endocrine effects of the dermorphin homologues examined. In fact, shorter dermorphins whose analgesic potency was directly related to the number of amino acids, exhibited an opposite pattern in evoking endocrine effects.
D000700:Analgesics; D000818:Animals; D001001:Anura; D001522:Behavior, Animal / Q000187:drug effects; D002369:Castration; D005260:Female; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018847:Opioid Peptides; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D013329:Structure-Activity Relationship
D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D009270:Naloxone; D011388:Prolactin; D007986:Luteinizing Hormone