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α1A and α1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex

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Summary

We have studied the role of α1A and α1B-adrenoceptors in noradrenaline- and methoxamine-stimulated inositol phosphate accumulation in rat renal cortical slices. [3H]Prazosin binding studies with and without inactivation of α1B-adrenoceptors by chloroethylclonidine treatment suggested that noradrenaline lacks relevant selectivity for α1-adrenoceptor subtypes. Both agonists stimulated [3H]inositol phosphate accumulation with similar maximal effects. The α1A-selective antagonists 5-methyl-urapidil and (+)-niguldipine inhibited inositol phosphate formation by both agonists with shallow biphasic curves but the high affinity component was only 15%–31% and 38%–41%, respectively. The irreversible α1B-selective antagonist chloroethylclonidine inhibited inositol phosphate generation by both agonists by 54%–57%. In contrast to our previous data in rat cerebral cortical slices; we conclude that in rat renal cortex both α1A- and α1B-adrenoceptors are involved in noradrenaline-and methoxamine-stimulated inositol phosphate generation.

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References

  • Baron BM, Siegel BW (1990) p-[125I]Iodoclonidine, a novel radiolabeled agonist for studying central α2-adrenergic receptors. Mol Pharmacol 38:348–356

    Google Scholar 

  • Boer R, Grassegger A, Schudt C, Glossmann H (1989) (+)-Niguldipine binds with very high affinity to Ca2+ channels and to a subtype of α1-adrenoceptors. Eur J Pharmacol 172:131–145

    Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Google Scholar 

  • Bylund DB (1992) Subtypes of α1 and α2-adrenergic receptors. FASEB J 6:832–839

    Google Scholar 

  • Clarke DE, Vimont RL, Blue DR jr (1990) Vascular alpha1-adrenoceptors in rat kidney: agonist and antagonist [prazosin, idazoxan, WB 4101, (+)-niguldipine] characterization. Eur J Pharmacol 183:733 (Abstr)

    Google Scholar 

  • Cotecchia S, Schwinn DA, Randall RR, Lefkowitz RJ, Caron MG, Kobilka BK (1988) Molecular cloning and expression of the cDNA for the hamster α1-adrenergic receptor. Proc Natl Acad Sci USA 85:7159–7163

    Google Scholar 

  • Feng F, Pettinger WA, Abel PW, Jeffries WB (1991) Regional distribution of α1-adrenoceptor subtypes in rat kidney. J Pharmacol Exp Ther 258:263–268

    Google Scholar 

  • Feth F, Rascher W, Michel MC (1991) G-Protein coupling and signalling of Y1-like neuropeptide Y receptors in SK-N-MC cells. Naunyn-Schmiedeberg's Arch Pharmacol 344:1–7

    Google Scholar 

  • Gross G, Hanft G, Rugevics C (1988) 5-Methyl-urapidil discriminates between subtypes of the α1-adrenoceptor. Eur J Pharmacol 151:333–335

    Google Scholar 

  • Gross G, Hanft G, Mehdorn HM (1989) Demonstration of α1A- and α1B-adrenoceptor binding sites in human brain tissue. Eur J Pharmacol 169:325–328

    Google Scholar 

  • Han C, Abel PW, Minneman KP (1987) α1-Adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature 329:333–335

    Google Scholar 

  • Han C, Wilson KM, Minneman KP (1990) α1-Adrenergic receptor subtypes and formation of inositol phosphates in dispersed hepatocytes and renal cells. Mol Pharmacol 37:903–910

    Google Scholar 

  • Han C, Minneman KP (1991) Interaction of subtype-selective antagonists with α1-adrenergic receptor binding sites in rat tissues. Mol Pharmacol 40:531–538

    Google Scholar 

  • Hanft G, Gross G (1989) Subclassification of al-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists. Br J Pharmacol 97:691–700

    Google Scholar 

  • Hanft G, Gross G (1990) The effect of reserpine, desipramine and thyroid hormone on α1a- and α1b-adrenoceptor binding sites: evidence for a subtype-specific regulation. Br J Clin Pharmacol 30 [Suppl]:125S–127S

  • Harrison JK, Pearson WR, Lynch KR (1991) Molecular characterization of α1 and α2-adrenoceptors. Trends Pharmacol Sci 12:62–67

    Google Scholar 

  • Jackson CA, Michel MC, Insel PA (1992) Expression of renal α1-adrenergic receptor subtypes in established hypertension. J Cardiovasc Pharmacol 19:857–862

    Google Scholar 

  • Kitamura Y, Imai S-I, Matsueda R, Nomura Y (1990) Effects of sulfhydryl-modifying reagents, 3-nitro-pyridinesulfenyl compounds, on the coupling between inhibitory receptors and GTP-binding proteins Gi/Go in rat brain membranes. Mol Pharmacol 38:184–191

    Google Scholar 

  • Klijn K, Slivka SR, Bell K, Insel PA (1991) Renal α1-adrenergic receptor subtypes: MDCK-D1 cells, but not rat cortical membranes possess a single population of receptors. Mol Pharmacol 39:407–413

    Google Scholar 

  • Lomasney JW Cotecchia S, Lorenz W, Leung WY, Schwinn DA, Yang-Feng TL, Brownstein M, Lefkowitz RJ, Caron MG (1991) Molecular cloning and expression of the cDNA for the α1A-adrenergic receptor. The gene for which is located on human chromosome 5. J Biol Chem 266:6365–6369

    Google Scholar 

  • Michel MC, Brodde O-E, Schnepel B, Behrendt J, Tschada R, Motulsky HJ, Insel PA (1989) [3H]Idazoxan and some other α2-adrenergic drugs also bind with high affinity to a non-adrenergic site. Mol Pharmacol 35:324–330

    Google Scholar 

  • Michel MC, Hanft G, Gross G (1990a) α1B-but not α1A-adrenoceptors mediate inositol phosphate generation. Naunyn-Schmiedeberg's Arch Pharmacol 341:385–387

    Google Scholar 

  • Michel MC, Knowlton KU, Gross G, Chien KR (1990b) α1-Adrenergic receptor subtypes mediate distinct functions in adult and neonatal rat heart. Circulation 82 [Suppl]:III-561 (Abstr)

    Google Scholar 

  • Michel MC, Philipp T, Brodde O-E (1992a) α- and β-adrenoceptors in hypertension: molecular biology and pharmacological studies. Pharmacol Toxicol 70 [Suppl II]:s1-s10

    Google Scholar 

  • Michel MC, Jäger S, Casto R, Rettig R, Graf C, Printz M, Insel PA, Philipp T, Brodde O-E (1992b) On the role of renal α-adrenergic receptors in spontaneously hypertensive rats. Hypertension 19:365–370

    Google Scholar 

  • Minneman KP (1988) α1-Adrenergic receptor subtypes, inositol phosphates, and sources of cell Ca2+. Pharmacol Rev 40:87–119

    Google Scholar 

  • Minneman KP, Han C, Abel PW (1988) Comparison of α1-adrenergic receptor subtypes distinguished by chloroethylclonidine and WB 4101. Mol Pharmacol 33:509–514

    Google Scholar 

  • Minneman KP, Atkinson B (1991) Interaction of subtype-selective antagonists with α1-adrenergic receptor-mediated second messenger responses in rat brain. Mol Pharmacol 40:523–530

    Google Scholar 

  • Perez DM, Piascik MT, Graham RM (1991) Solution-phase library screening for the identification of rare clones: isolation of an α1D-adrenergic receptor cDNA. Mol Pharmacol 40:876–883

    Google Scholar 

  • Robinson JP, Kendall DA (1990) Niguldipine discriminates between α1-adrenoceptor-mediated second messenger responses in rat cerebral cortex slices. Br J Pharmacol 100:3–4

    Google Scholar 

  • Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann N Y Acad Sci 51:660–672

    Google Scholar 

  • Schwinn DA, Lomasney JW, Lorenz W, Szklut PJ, Fremeau RT, Yang-Feng TL, Caron MG, Lefkowitz RJ, Cotecchia S (1990) Molecular cloning and expression of the cDNA for a novel α1-adrenergic receptor. J Biol Chem 265:8183–8189

    Google Scholar 

  • Sonnenburg WK, Zhu J, Smith WL (1990) A prostaglandin E receptor coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rabbit cortical collecting tubule cells. J Biol Chem 265:8479–8483

    Google Scholar 

  • Suzuki E, Tsujimoto G, Tamura K, Hashimoto K (1990) Two pharmacologically distinct α1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role. Mol Pharmacol 38:725–736

    Google Scholar 

  • Tsujimoto G, Tsujimoto A, Suzuki E, Hashimoto K (1989) Glycogen phosphorylase activation by two different α1-adrenergic receptor subtypes: methoxamine selectively stimulates a putative α1-adrenergic receptor subtype (α1a) that couples with Ca2+ influx. Mol Pharmacol 36:166–176

    Google Scholar 

  • Wilson KM, Minneman KP (1990a) Pertussis toxin inhibits norepinephrine-stimulated inositol phosphate formation in primary brain cell cultures. Mol Pharmacol 38:274–281

    Google Scholar 

  • Wilson KM, Minneman KP (1990b) Different pathways of [3H]inositol phosphate formation mediated by α1A- and α1B-adrenergic receptors. J Biol Chem 265:17601–17606

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Essen, W-4300, Essen, Federal Republic of Germany

    Martin C. Michel, Rainer Büscher, Thomas Philipp & Otto-Erich Brodde

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  1. Martin C. Michel
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  2. Rainer Büscher
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  3. Thomas Philipp
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  4. Otto-Erich Brodde
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Michel, M.C., Büscher, R., Philipp, T. et al. α1A and α1B-adrenoceptors enhance inositol phosphate generation in rat renal cortex. Naunyn-Schmiedeberg's Arch Pharmacol 347, 180–185 (1993). https://doi.org/10.1007/BF00169264

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  • DOI: https://doi.org/10.1007/BF00169264

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