Modulation der renalen Transmitter-Freisetzung durch präsynaptische Rezeptoren

Rump, L. C.; Schollmeyer, P.

doi:10.1007/bf01717341

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…A possible explanation of these data would be the existence of a prejunctional q-adrenoceptor which inhibits noradrenaline release and thereby reduces Padrenoceptor mediated stimulation of renin release in the human kidney; however, alternative explanations are possible. It is well documented that activation of prejunctional a2-adrenoceptors inhibits noradrenaline release in animal kidneys (Rump, 1987;Rump and Schollmeyer, 1989). This inhibitory effect is more pronounced when the firing rate of the renal nerves is low (Rump and Majewski, 1987;Bohmann et al, 1993b).…”

Section: Effects Of Renal A-adrenoceptor Stimulationmentioning

confidence: 99%

α‐Adrenergic regulation of human renal function

Michel

1996

Fundamemntal Clinical Pharma

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Pharmacological and molecular cloning techniques have identified six human subtypes of alpha-adrenoceptors which are designated alpha 1A, alpha 1D, alpha 2A, and alpha 2C. At the protein level human kidney expresses predominantly alpha 2A-adrenoceptors while other alpha 2-adrenoceptor subtypes or alpha 1-adrenoceptors have not been detected consistently in radioligand binding studies. However, the presynaptic receptors, which inhibit noradrenaline release in the human kidney, appear to belong to the alpha 2C-subtype. Intrarenal infusion of the nonselective alpha-adrenoceptor antagonist, phentolamine, and of the selective alpha 2-adrenoceptor antagonist, yohimbine, but not of the selective alpha 1-adrenoceptor antagonist, doxazosin, increase renal blood flow and renin release in hypertensive patients undergoing diagnostic renal angiography. Thus, alpha 2- but not alpha 1-adrenoceptors appear to mediate a tonic renal vasoconstriction and inhibition of renin release. Effects of systemically given alpha 1-adrenoceptor agonists and antagonists are difficult to interpret on a mechanistic level since direct effects in the kidney and indirect effects due to baroreflex activation and peripheral presynaptic and central sympatholytic actions may at least partially offset each other. Moreover, some of these drugs may additionally act independent of alpha-adrenoceptors, for example, via imidazoline recognition sits. The net result in a given subject may depend on the endogenous sympatho-adrenal tone. Thus, for each target population of interest, effects have to be described empirically for each drug.

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Section: Effects Of Renal A-adrenoceptor Stimulationmentioning

confidence: 99%

α‐Adrenergic regulation of human renal function

Michel

1996

Fundamemntal Clinical Pharma

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“…The sympathetic axons in the kidney are endowed with a variety of prejunctional receptors which when activated enhance or inhibit transmitter release (Starke, 1987; Rump, 1987; Rump & Schollmeyer, 1989; Starke et al , 1989; Bohmann et al , 1993a,b). These prejunctional receptors include α 2 ‐adrenoceptors activated by noradrenaline (see Starke, 1987; Starke et al , 1989) and P 1 ‐receptors of the A 1 ‐subtype activated by adenosine (see Fredholm & Dunwiddie, 1988); both of these receptors mediate inhibition of transmitter release.…”

Section: Introductionmentioning

confidence: 99%

P₂‐receptor modulation of noradrenergic neurotransmission in rat kidney

Böhmann

Kügelgen

Rump

1997

British J Pharmacology

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1 ATP has previously been shown to act as a sympathetic cotransmitter in the rat kidney. The present study analyses the question of whether postganglionic sympathetic nerve endings in the kidney possess P 2 -receptors which modulate noradrenaline release. Rat kidneys were perfused with Krebs-Henseleit solution containing the noradrenaline uptake blockers cocaine and corticosterone and the a 2 -adrenoceptor antagonist rauwolscine. The renal nerves were electrically stimulated, in most experiments by 30 pulses applied at 1 Hz. The out¯ow of endogenous noradrenaline (or, in some experiments, of ATP and lactate dehydrogenase) as well as the perfusion pressure were measured simultaneously. 2 The P 2 -receptor agonist adenosine-5'-O-(3-thiotriphosphate) (ATPgS, 3 ± 30 mM) reduced the renal nerve stimulation (RNS)-induced out¯ow of noradrenaline (estimated EC 50 =8 mM). The P 2 -receptor antagonist cibacron blue 3GA (30 mM) shifted the concentration-inhibition curve for ATPgS to the right (apparent pK B value 4.7). 3 Cibacron blue 3GA (3 ± 30 mM) and its isomer reactive blue 2 (3 ± 30 mM) signi®cantly increased RNSinduced out¯ow of noradrenaline in the presence of the P 1 -receptor antagonist 8-(p-sulphophenyl)theophylline (8-SPT, 100 mM) by about 70% and 90%, respectively. The P 2 -receptor antagonist suramin (30 ± 300 mM) only tended to enhance RNS-induced out¯ow of noradrenaline. When the nerves were stimulated by short pulse trains consisting of 6 pulses applied at 100 Hz (conditions under which autoinhibition is inoperative), reactive blue 2 did not aect the RNS-induced out¯ow of noradrenaline. 4 RNS (120 pulses applied at 4 Hz) induced the out¯ow of ATP but not of the cytoplasmatic enzyme lactate dehydrogenase. 5 ATPgS (3 ± 30 mM) concentration-dependently reduced pressor responses to RNS at 1 Hz. Cibacron blue 3GA, reactive blue 2 as well as suramin also reduced pressor responses to RNS (maximally by 50 to 70%). 6 This study in rat isolated kidney, in which the release of endogenous noradrenaline was measured, demonstrates that renal sympathetic nerves possess prejunctional P 2 -receptors that mediate inhibition of transmitter release. These prejunctional P 2 -receptors are activated by endogenous ligands, most likely ATP, released upon nerve activity. Both, P 2 -receptor agonists and P 2 -receptor antagonists reduced pressor responses to RNS either by inhibiting transmitter release or by blocking postjunctional vasoconstrictor P 2 -receptors.

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Effects of imidazolines on noradrenaline release in rat isolated kidney

Böhmann

Schollmeyer

Rump

1994

Naunyn-Schmiedeberg's Arch Pharmacol

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The aim of the present study was to investigate whether or not activation of imidazoline receptors modulates noradrenaline release in the rat isolated kidney. Kidneys were pre-exposed to 3H-noradrenaline and the renal nerves were stimulated with 6 pulses at 100 Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of endogenous noradrenaline release. The imidazoline derivatives clonidine (1-1000 nmol/l) and moxonidine (10-1000 nmol/l) inhibited S-I outflow of radioactivity with an EC50 of 6.8 nmol/l and 62.5 nmol/l and a maximum of 88% and 97%, respectively. The concentration response curves for clonidine and moxonidine were shifted to the right by the selective alpha 2-adrenoceptor antagonist rauwolscine (0.1 mumol/l) in a parallel manner with identical pKB's of 8.52 and 8.46, respectively. Furthermore, the alpha-adrenoceptor agonist (-)-alpha-methylnoradrenaline (0.1-30 nmol/l), which has no affinity for imidazoline binding sites, inhibited S-I outflow of radioactivity with and EC50 of 2.4 nmol/l and a maximum of 94%. Rauwolscine (0.1 mumol/l) again shifted the concentration response curve for this alpha-adrenoceptor agonist to the right with a pKB of 8.40. Moreover, the selective alpha 2-adrenoceptor antagonist 2-[2-(2-methoxy-1,4- benzo-dioxanyl)]imidazoline HCl (RX821002, 0.01 mumol/l) shifted the concentration response curves for clonidine and moxonidine to the right with pKB's of 9.46 and 9.18, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Modulation der renalen Transmitter-Freisetzung durch präsynaptische Rezeptoren

Cited by 7 publications

References 31 publications

α‐Adrenergic regulation of human renal function

α‐Adrenergic regulation of human renal function

P₂‐receptor modulation of noradrenergic neurotransmission in rat kidney

Effects of imidazolines on noradrenaline release in rat isolated kidney

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Modulation der renalen Transmitter-Freisetzung durch präsynaptische Rezeptoren

Cited by 7 publications

References 31 publications

α‐Adrenergic regulation of human renal function

α‐Adrenergic regulation of human renal function

P2‐receptor modulation of noradrenergic neurotransmission in rat kidney

Effects of imidazolines on noradrenaline release in rat isolated kidney

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P₂‐receptor modulation of noradrenergic neurotransmission in rat kidney