ISSN:
1432-1912
Keywords:
Uptake of tyramine
;
Indirectly acting amines
;
Extravesicular binding
;
Neuronal efflux of noradrenaline
;
Compartment analysis
;
Rabbit heart
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1) In isolated perfused hearts of reserpine (R)-and pargyline (P)-pretreated rabbits (i.e. RP-hearts) initial rates of intracellular uptake of 14C-tyramine and of 3H-amphetamine were measured as described by Graefe et al. (1978). The uptake of 14C-tyramine, but not that of 3H-amphetamine was inhibited by cocaine. 2) Saturation kinetics of the intracellular uptake of 14C-tyramine revealed a non-saturable (diffusional) and a saturable (carrier-mediated) component of uptake. 3) After 30 min of perfusion with 14C-tyramine the accumulated 14C-radioactivity in RP-hearts consisted of unchanged tyramine (about 60%), octopamine (about 30%) and deaminated metabolites (about 10%). In contrast, 14C-octopamine was the main radioactive substance when the perfusion with 14C-tyramine was followed by 100 min of wash-out. 4) IC50-Values of tyramine, amphetamine, amantadine and nomifensine for inhibition of neuronal uptake of 3H-noradrenaline were determined in RPU-hearts (i.e. in RP-hearts whose COMT was inhibited by U-0521). 5) About equieffective concentrations (with respect to inhibition of 3H-noradrenaline uptake) of tyramine, amphetamine, amantadine and noradrenaline (i.e. of substrates of the neuronal amine carrier) caused a pronounced (and comparable) release of 3H-noradrenaline from RPU-hearts, whereas cocaine and nomifensine (i.e. uptake inhibitors) caused only a very small release. Low sodium caused a release comparable to that induced by substrates of the amine carrier. 6) Increasing concentrations of tyramine (0.2–24 μmol/l) caused mobilization of 3H-noradrenaline from a small “bound fraction” and partial mobilization from a large compartment which was characterized by a rate constant for efflux of about 0.014 min−1 (compartment I). The peak-value of the tyramine-induced efflux of 3H-noradrenaline exhibited saturability with increasing concentrations of tyramine. Half-maximal release was observed at a tyramine concentration which corresponded to a) the IC50-value for inhibition of uptake of 3H-noradrenaline and b) the K m of the saturable component of uptake of 14C-tyramine. 7) That part of neuronally accumulated 3H-noradrenaline (mainly in compartment I) which was not further mobilized by high concentrations of tyramine was also hardly mobilized by veratridine (in the absence of Ca2+). However, in the presence of Ca2+, veratridine as well as nicotine induced a release of this “tyramine-resistant” 3H-noradrenaline. 8) It is concluded that in RPU-hearts the distribution of 3H-noradrenaline within the partially “tyramine-resistant” compartment I and within the “bound fraction” might represent 3H-noradrenaline “trapped” within the acid interior of “reserpinized” vesicles and within a small population of intact storage vesicles, respectively. The fast release of 3H-noradrenaline (from RPU-hearts) by tyramine, noradrenaline, amphetamine and amantadine might be caused by facilitation of the outward transport of axoplasmic noradrenaline; the extend of facilitation may be directly connected to the velocity of uptake of these substrates by the amine carrier.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00497669
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