ABSTRACT

The originally described cDNA of the turkey -adrenergic receptor encodes a receptor with a carboxyl-terminal, 59-amino acid extension that was not found in several mammalian - adrenergic receptors. This extension blocks agonist-promoted endocytosis and down-regulation of the receptor. This carboxyl-terminal domain is encoded by an exon distinct from that which encodes the body of the receptor, and the originally described cDNA results from removal of an 849-nucleotide intron. Unspliced mRNA encodes a shorter open reading frame whose translated carboxyl terminus is identical with that of the mammalian -adrenergic receptors. There is no evidence for other introns in the coding region. Splicing of the intron to produce the nonendocytosing receptor is highest in fetal blood cells, is appreciable in adult brain and heart, and is detectable in other tissues. Thus, different tissues use alternative splicing to express -adrenergic receptors that either do or do not endocytose and down-regulate in response to agonist.

FOOTNOTES

*

This work was supported by a postdoctoral fellowship from Cadus Pharmaceuticals, Inc., National Institutes of Health Grant R37GM30355, and Robert A. Welch Foundation Grant I-0982. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) U14958[GenBank].

§

To whom correspondence and reprint requests should be addressed: Dept. of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9041.

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Turkeys express at least three -adrenergic receptor subtypes: the subtype discussed here, a subtype(45) , and a third subtype denoted ``4C'' (which is probably not analogous to the mammalian ; (45) ). The receptor described here is based on the predominance of its pharmacologic specificity, although it differs somewhat from mammalian -adrenergic receptors in its affinities for some synthetic ligands(48) . Its membrane spans and short interspan loops share 81% amino acid identity with mammalian -adrenergic receptors but only 64% identity with the mammalian isoform. (The mammalian isoform is similarly 64% identical with the mammalian in these regions.) Last, the overall structure of the turkey -adrenergic receptor gene is strikingly similar to that of the rat and monkey -adrenergic receptor genes (this work).

()

The abbreviations used are: PCR, polymerase chain reaction; RT-PCR, reverse transcriptase PCR amplification of cDNA synthesized from poly(A) RNA samples; ORF, open reading frame; bp, base pair(s).

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