Identification of alpha 1-adrenoceptor subtypes present in the human prostate
| Autor: | G. Vallancien, S.Z. Langer, C. Faure, David I. Graham, C. Pimoule |
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| Rok vydání: | 1994 |
| Předmět: |
Adenoma
Male medicine.medical_specialty Oxymetazoline Molecular Sequence Data Biology Transfection Tritium Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Radioligand Assay Non-competitive inhibition Internal medicine Complementary DNA Cricetinae Receptors Adrenergic alpha-1 medicine Animals Humans Northern blot Amino Acid Sequence RNA Messenger General Pharmacology Toxicology and Pharmaceutics Cloning Molecular DNA Primers chemistry.chemical_classification Messenger RNA Base Sequence Sequence Homology Amino Acid Cell Membrane Prostate Brain Prostatic Neoplasms Muscle Smooth General Medicine Smooth muscle contraction Prazosin Blotting Northern Molecular biology Reverse transcriptase Amino acid Rats Kinetics Endocrinology chemistry Cattle medicine.drug HeLa Cells |
| Zdroj: | Life sciences. 54(21) |
| ISSN: | 0024-3205 |
| Popis: | α 1 -Adrenoceptors (ARs) play an important role in mediating human prostatic smooth muscle contraction. In the present study cDNA fragments covering different domains of 3 α 1 -AR subtypes ( α 1b , α 1c and α 1d ) were generated from human prostate by reverse transcription coupled to the polymerase chain reaction (RT-PCR). The reconstituted partial sequence (349 amino acids) of the human prostatic α 1c-AR PCR products showed 94% identity at the amino acid level with that of the corresponding region of the cloned bovine brain α 1c -AR. Using human α 1 -AR subtype selective cDNA probes in Northern blot analysis, the co-expression of mRNA transcripts corresponding to α 1b -, α 1c - and α 1d -AR subtypes was detected in 4 different regions (apex, base, periurethra and lateral lobe) of the human prostate. Competitive inhibition experiments of [ 3 H]-prazosin binding to membrane preparations of human prostate revealed that the non-selective α 1 -subtype antagonist, alfuzosin, produced a monophasic inhibition curve, whereas oxymetazoline produced a 2-component inhibition curve with pK i values of 8.54 and 5.46. The high-affinity α 1 -AR component of the oxymetazoline inhibition curve was predominant (57%–66%) and showed an affinity for oxymetazoline comparable to that of the α 1 c -AR subtype. As such our results illustrate the expression of different α 1 -AR subtypes in human prostate and importantly that α 1c represents the predominant α 1 -AR subtype present in this tissue. |
| Databáze: | OpenAIRE |
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