MODULATION OF RENAL NORADRENALINE RELEASE BY PREJUNCTIONAL RECEPTOR SYSTEMS <i>IN VITRO</i>

Rump, L. C.

doi:10.1111/j.1440-1681.1987.tb00993.x

Cited by 16 publications

(5 citation statements)

References 21 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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“…Sympathetic nerve terminals possess prejunctionally located receptors which when activated can modulate the amount of noradrenaline released per nerve impulse (Rand et al, 1980). Prejunctional modulation of renal noradrenaline release has been mainly studied in isolated kidneys of either rat (Rump, 1987) or rabbit.…”

Section: Introductionmentioning

confidence: 99%

Modulation of noradrenaline release from rat cortical kidney slices: effects of angiotensin I and II.

Rump

Schuster

Wilde

et al. 1990

Brit J Clinical Pharma

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Rat kidney slices were incubated with [3H]-noradrenaline and placed into a superfusion chamber between two platinum electrodes. The kidney slices accumulated and stored radioactivity. In kidney slices taken from rats whose sympathetic nerve terminals were destroyed by pretreatment with 6-hydroxydopamine accumulation of radioactivity was abolished. The a2-adrenoceptor antagonist idazoxan (0.1-1 F.M) enhanced but tetrodotoxin (TTX, 1 ,LM) or omission of calcium from the superfusion solution abolished the stimulation induced (S-I) outflow of radioactivity. Angiotensin (A) I (3-300 nM) and AII (1-100 nM) enhanced S-I outflow of radioactivity. The effect of AI was markedly attenuated by the angiotensin converting enzyme inhibitor captopril (3 FLM) and that of AII was blocked by the AII receptor antagonist saralasin (1 FLM). These results suggest that the kidney slice preparation is a valid technique to study modulation of renal noradrenaline release. Endogenous noradrenaline released from sympathetic nerves in rat kidney slices activates prejunctional a2-adrenoceptors to inhibit its own release. AII, which can also be formed locally from AI in these kidney slices, activates prejunctional AII receptors to facilitate renal noradrenaline release.

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“…The antagonists alone had no effect on overflow at the concentrations studied. (Rump, 1987); (3) active removal of NA or P-adrenoceptor agents, and (4) endogenous factors generated in the organ, especially angiotensin II and prostaglandins in the present case (Boke & Malik, 1983;Malik, 1988). Therefore, care was taken in the present study to minimize the influence of these factors.…”

Section: Autoradiographymentioning

confidence: 89%

Pharmacological characterization and anatomical localization of prejunctional β‐adrenoceptors in the rat kidney

Lakhlani

Amenta

Napoleone

et al. 1994

British J Pharmacology

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1 The subtype and anatomical localization of P-adrenoceptors mediating facilitation of stimulusinduced overflow of noradrenaline ('prejunctional P-adrenoceptors') are not conclusively known to date.The present study was undertaken to characterize these receptors by use of pharmacological methods as well as to define their localization (prejunctional or postjunctional) with radio-ligand binding and autoradiography techniques combined with surgical denervation of the sympathetic innervation to the rat kidney.2 Exposure of the kidney to (-)-isoprenaline, the nonselective P-adrenoceptor agonist, resulted in a dose-dependent facilitation of stimulus-induced neurotransmitter overflow. This response was inhibited by propranolol, the f,-and P2-adrenoceptor antagonist, with a pA2 of 9.20 suggesting that the prejunctional P-adrenoceptors are not of the P3-subtype. 3 The rank order of potency and potency ratios of P-adrenoceptor agonists at renal prejunctional P-adrenoceptors (EC50 for agonist/EC50 for (-)-isoprenaline) were: (-)-isoprenaline (1) >procaterol (2) > salbutamol (3) >adrenaline (10) > (+)-isoprenaline (25). However, dobutamine, the Pf-adrenoceptor agonist, failed to enhance stimulus-induced overflow of noradrenaline. These results are indicative of the presence of P2-adrenoceptors as prejunctional ,-adrenoceptors. 4 Facilitation elicited by (-)-isoprenaline and procaterol, the selective P2-adrenoceptor agonist, was inhibited by ICI 118,551, the selective P2-adrenoceptor antagonist, with pKb values of 9.20 and 9.35, respectively at renal prejunctional P-adrenoceptors. Similarly, the pKb values of metoprolol, the selective fi-adrenoceptor antagonist, at renal prejunctional P-adrenoceptors were determined to be 6.25 and 6.18 against (-)-isoprenaline and procaterol, respectively. These results suggest the presence of a homogeneous population of P2-adrenoceptors as prejunctional P-adrenoceptors. 5 Radio-ligand binding analysis of renal P-adrenoceptors revealed the prevalence of the fi,-subtype as compared to the P2-subtype (63% vs 37%). However, surgical denervation of the rat kidney, resulting in more than 90% reduction in renal noradrenaline content, selectively reduced the P2-adrenoceptor population by 80%, implying the presence of P2-adrenoceptors on renal sympathetic nerve terminals.6 Autoradiographic analysis demonstrated the presence of P,-adrenoceptors on cortical structures such as glomeruli and tubules. fi2-Adrenoceptors were found to be present on tubules (minor population), collecting tubules in outer medulla and the adventitia and adventitial-medial border of intraparenchymal branches of the renal artery. Surgical denervation of the rat kidney resulted in the disappearance of P2-adrenoceptors associated with the intraparenchymal branches, without affecting the P-adrenoceptor populations at other sites. These results support the notion that the P2-subtype is present on renal sympathetic nerve terminals and demonstrate that these prejunctional P2-adrenoceptors are associated with the renal vasculature ...

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MODULATION OF RENAL NORADRENALINE RELEASE BY PREJUNCTIONAL RECEPTOR SYSTEMS IN VITRO

Cited by 16 publications

References 21 publications

α‐Adrenergic regulation of human renal function

α‐Adrenergic regulation of human renal function

Modulation of noradrenaline release from rat cortical kidney slices: effects of angiotensin I and II.

Pharmacological characterization and anatomical localization of prejunctional β‐adrenoceptors in the rat kidney

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