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No inotropic action of enkephalins or enkephalin derivatives on electrically‐stimulated atria isolated from lean and obese rats
Author(s) -
Saunders W.S.,
Thornhill J.A.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08888.x
Subject(s) - isoprenaline , enkephalin , carbachol , endocrinology , medicine , chemistry , stimulation , receptor , opioid
1 Inotropic actions of the endogenous enkephalins, leucine enkephalin ([Leu] enkephalin) and methionine enkephalin ([Met] enkephalin), and derivatives, [D‐Ala 2 ‐methionine] enkephalinamide (DAMEA) and [D Ala 2 ‐leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (±)‐isoprenaline or carbachol, on electrically‐stimulated atria excised from Sprague‐Dawley, fatty, Zucker (fa/fa) and lean, hooded heterozygous (Fa/fa) rats. 2 [Met] enkephalin, [Leu] enkephalin, DAMEA and DALEA (4 × 10 −7 M to 4 × 10 −4 M) caused no significant changes in atrial tension in any group compared to pre‐injection control values or those following the infusion of Krebs‐Henseleit control solution. 3 NA and isoprenaline (10 −7 to 10 −6 M) caused significant, dose‐related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development. [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 × 10 −6 M) infused concurrently with NA or isoprenaline (10 −6 M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone. 4 Carbachol (10 −9 and 10 −8 M) caused a dose‐related decrease (10% and 30–40%, respectively, from pre‐injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 × 10 −6 M) together with carbachol (10 −8 M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone. 5 The results indicate that the endogenous pentapeptides, ([Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically‐stimulated auricles isolated from Sprague‐Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo , the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility.