The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition

@article{Fuder1983TheDO,
  title={The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition},
  author={Hermann Fuder and Erich Muscholl and R Spemann},
  journal={British Journal of Pharmacology},
  year={1983},
  volume={79}
}
1 Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]‐(—)‐noradrenaline. The nerves were stimulated with up to 40 trains of 10 pulses every min at 1 Hz, and the evoked increases of [3H]‐noradrenaline overflow into the perfusate, of right atrial tension development and ventricular beating frequency were measured. 2 Oxymetazoline inhibited the evoked transmitter overflow (IC50: 10 nM) and decreased the postsynaptic responses in a concentration‐dependent… 
The determination of presynaptic KA values of methacholine and pilocarpine and of a presynaptic receptor reserve in the rat perfused heart.
TLDR
Results show that KA values for methacholine and pilocarpine obtained at presynaptic receptors are similar to those obtained at postsynaptic muscarinic receptors, in agreement with the idea that mus carinic receptors located on postganglionic adrenergic nerves are not different from those located on effector sites of non-neuronal tissue.
Autoinhibition of noradrenaline release from the rat heart as a function of the biophase concentration. Effects of exogenous α-adrenoceptor agonists, cocaine, and perfusion rate
TLDR
The results indicate that the α2-adrenoceptor-mediated autoin inhibition in the rat perfused heart depends on the clearance of transmitter from the biophase via neuronal reuptake and diffusion into the vascular space, thus increasing the autoinhibition of release.
Further study of prerequisites for the enhancement by α-adrenoceptor antagonists of the release of noradrenaline
TLDR
The results demonstrate that the enhancement by α-adrenoceptor antagonists of the release of noradrenaline depends on the biophase concentration of norADrenaline, which is not shared by at least one other release-enhancing drug, namely TEA.
Estimation ofpA2 values at presynaptic α2-autoreceptors in rabbit and rat brain cortex in the absence of autoinhibition
TLDR
The experiments confirm that pA2 values determined under conditions of autoinhibition are too low and suggest that α2-adrenoceptors in rabbit brain cortex differ slightly from those in rat brain cortex.
Receptor protection experiments confirm the identity of presynaptic α2-autoreceptors
TLDR
It is concluded that drugs with affinity for α2-adrenoceptors protect the noradrenergic axons of rabbit brain cortex against the long-lasting release-enhancing effect of phenoxybenzamine.
Affinity and efficacy of racemic, (+)‐, and (−)‐methacholine in muscarinic inhibition of [3H]‐noradrenaline release
TLDR
The results show that, in the effector system of presynaptic muscarinic inhibition, methacholine enantiomers differ greatly not only in affinity for the receptor, but also to some extent in the efficiency of signal transmission, and both parameters contribute to the high isomeric potency ratio.
Phentolamine—an unexpected agonist in the rabbit
TLDR
These rabbit‐specific agonist effects of phentolamine at sites similar to α2‐adrenoceptors make this drug unsuitable as an α‐adRenoceptor antagonist in rabbits.
α2c‐Adrenoceptor‐modulated release of noradrenaline in human right atrium
TLDR
The α2C classification possibly separates, in general, human α2‐autoreceptors from those in lagomorph (rabbit, mouse, guinea pig) species that have been proposed to be predominantly α2A or α2D.
P2-Receptor-mediated inhibition of noradrenaline release in the rat pancreas
TLDR
The results indicate that the postganglionic sympathetic axons of the rat pancreas possess A1-adenosine and P2-receptors, which are activated by an endogenous ligand, presumably ATP, during appropriate trains of action potentials.
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