Pharmacological characterization and anatomical localization of prejunctional β‐adrenoceptors in the rat kidney
Authors: Lakhlani Parul P. , Amenta Francesco , Napoleone Paolo , Felici Laura , Eikenburg Douglas C. 
Published: July 2012

The subtype and anatomical localization of β‐adrenoceptors mediating facilitation of stimulus‐induced overflow of noradrenaline (‘prejunctional β‐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.

Exposure of the kidney to (–)‐isoprenaline, the nonselective β‐adrenoceptor agonist, resulted in a dose‐dependent facilitation of stimulus‐induced neurotransmitter overflow. This response was inhibited by propranolol, the β1 and β2‐adrenoceptor antagonist, with a pA2 of 9.20 suggesting that the prejunctional β‐adrenoceptors are not of the β3‐subtype.

The rank order of potency and potency ratios of β‐adrenoceptor agonists at renal prejunctional β‐adrenoceptors (EC50 for agonist/EC50 for (–)‐isoprenaline) were: (–)‐isoprenaline (1) > procaterol (2) > salbutamol (3) > adrenaline (10) > (+)‐isoprenaline (25). However, dobutamine, the β1‐adrenoceptor agonist, failed to enhance stimulus‐induced overflow of noradrenaline. These results are indicative of the presence of β2‐adrenoceptors as prejunctional β‐adrenoceptors.

Facilitation elicited by (–)‐isoprenaline and procaterol, the selective β2‐adrenoceptor agonist, was inhibited by ICI 118,551, the selective β2‐adrenoceptor antagonist, with pKb values of 9.20 and 9.35, respectively at renal prejunctional β‐adrenoceptors. Similarly, the pKb values of metoprolol, the selective β1‐adrenoceptor antagonist, at renal prejunctional β‐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 β2‐adrenoceptors as prejunctional β‐adrenoceptors.

Radio‐ligand binding analysis of renal β‐adrenoceptors revealed the prevalence of the β1‐subtype as compared to the β2‐subtype (63% vs 37%). However, surgical denervation of the rat kidney, resulting in more than 90% reduction in renal noradrenaline content, selectively reduced the β2‐adrenoceptor population by 80%, implying the presence of β2‐adrenoceptors on renal sympathetic nerve terminals.

Autoradiographic analysis demonstrated the presence of β1‐adrenoceptors on cortical structures such as glomeruli and tubules. β2‐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 β2‐adrenoceptors associated with the intraparenchymal branches, without affecting the β‐adrenoceptor populations at other sites. These results support the notion that the β2‐subtype is present on renal sympathetic nerve terminals and demonstrate that these prejunctional β2‐adrenoceptors are associated with the renal vasculature and not with renal tubules.

The results of the present investigation demonstrate that renal prejunctional β‐adrenoceptors are of the β2‐subtype in nature. These receptors are present on sympathetic nerve terminals which are associated with the renal vasculature.