Regulatory properties of α1b-adrenergic receptors defective in coupling to phosphoinositide hydrolysis

Jiefa Wang, Lei Wang, Jodi L. Anderson, Nancy A. Schulte, Myron Lee Toews

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Previous studies have suggested that G protein coupling, phospholipase C activation, phosphoinositide hydrolysis, and protein kinase C activation may be required for α1B-adrenergic receptor regulation, particularly for their endocytosis into intracellular vesicles. Accordingly, the internalization and down-regulation properties of mutated receptors with defects in G protein coupling and second messenger generation were investigated. The Δ12 and Δ5 receptors, previously shown to be defective in G protein coupling, exhibited greater agonist-induced losses of cell surface accessibility assessed by radioligand binding to intact cells on ice than for the wild-type receptor; however, these receptors were completely defective in endocytosis into intracellular vesicles assessed by sucrose density gradient centrifugation. These receptors also did not undergo down-regulation with long-term agonist exposure as did the wild-type receptor; instead, a prominent up-regulation was observed. The Y348A receptor, previously shown to be defective in phosphoinositide hydrolysis and endocytosis was also defective in down-regulation but did not exhibit significant up-regulation. In contrast, a receptor construct with amino acid residues 246 to 261 deleted (Δ[246-261]) was also defective in stimulation of phosphoinositide hydrolysis but exhibited internalization and down-regulation properties essentially identical to those for the wild-type receptor. Together, these results suggest that stimulation of phosphoinositide hydrolysis by α1B-adrenergic receptors is not required for their endocytosis or down-regulation but that similar and overlapping receptor structural domains are involved in mediating these processes.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume300
Issue number1
DOIs
StatePublished - Jan 12 2002

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Phosphatidylinositols
Adrenergic Receptors
Endocytosis
Hydrolysis
Down-Regulation
GTP-Binding Proteins
Up-Regulation
1-Phosphatidylinositol 4-Kinase
Density Gradient Centrifugation
Ice
Type C Phospholipases
Second Messenger Systems
Protein Kinase C
Sucrose
Amino Acids

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Regulatory properties of α1b-adrenergic receptors defective in coupling to phosphoinositide hydrolysis. / Wang, Jiefa; Wang, Lei; Anderson, Jodi L.; Schulte, Nancy A.; Toews, Myron Lee.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 300, No. 1, 12.01.2002, p. 134-141.

Research output: Contribution to journalArticle

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