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  • Title: Mechanisms involved in the cardiovascular responses to opioid products of proenkephalin in the anaesthetised rat.
    Author: Douglas H, Kitchen I.
    Journal: Gen Pharmacol; 1992 Mar; 23(2):269-77. PubMed ID: 1639241.
    Abstract:
    1. Cardiovascular effects of opioid peptide products of proenkephalin, [Met] enkephalin (ME), [Leu] enkephalin (LE), [Met] enkephalyl Arg6-Phe7 (MEAP) and [Met] enkephalyl Arg6-Gly7-Leu8 (MEAGL) have been studied in urethane-anaesthetised rats. 2. ME, LE, MEAP and MEAGL produced vasodepression and bradycardia mediated by mu-opioid receptors. 3. Atypical responses to MEAP were observed in a quarter of the animals studied showing tachycardia and pressor effects. This response was probably due to the release of the dipeptide Arg-Phe which exerted its effects at sympathetic ganglia. 4. Studies with the peptidase inhibitors captopril and bestatin showed a differential potentiation of the cardiovascular effects of the proenkephalin products by inhibition of angiotensin converting enzyme and aminopeptidase. 5. The effects of vagotomy, pithing and studies with atropine, and N-methyl levallorphan were used to demonstrate that, for all four proenkephalin peptides, cardiovascular effects were mediated by peripheral opioid receptors and transmission to the CNS via vagal afferents.
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