Hypotensive effect of novel chimeric peptides of met-enkephalin and FMRFa.
Endogenous opioid peptides like endomorphins, met-enkephalin and NPFF/FMRFamide family of neuropeptides, besides playing a role in modulation of antinociception, also affect cardiovascular system. Based on MERF, which consists of overlapping sequences of FMRFa and met-enkephalin, two chimeric peptides YGGFMKKKFMRFamide (YFa) and [D-Ala2] YAGFMKKKFMRFamide ([D-Ala2] YFa) were designed and synthesized. In this study, effect of YFa and [D-Ala2] YFa on arterial blood pressure and heart rate was evaluated in anaesthetized rats. Both YFa and [D-Ala2] YFa showed a dose-dependent fall in mean arterial pressure in dose-range of 13-78 micromol/kg. After naloxone treatment (5 mg/kg), vasodepressor effect of [D-Ala2] YFa and YFa was only partially blocked as compared to met-enkephalin. Partial blockade of vasodepressive effect of YFa and [D-Ala2] YFa by naloxone may be attributed to interaction of these chimeric peptides with receptors other than naloxone-sensitive receptors such as anti-opioid receptors, adrenergic receptors and D-analogue receptors.
Hanif
Kashif
K
Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi-7, India.
Fahim
Mohammad
M
Pavar
Mahesh Chand
MC
Bansal
Vishal
V
Pasha
Santosh
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000737:chemistry*; D004745:Enkephalins / Q000378:metabolism; D019835:FMRFamide / Q000737:chemistry*; D006339:Heart Rate; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D004745:Enkephalins; D009479:Neuropeptides; D010455:Peptides; D011941:Receptors, Adrenergic; D011957:Receptors, Opioid; D014665:Vasodilator Agents; C034565:naloxone receptor; D009270:Naloxone; D004744:Enkephalin, Methionine; D019835:FMRFamide