α 1 adrenoceptor
The α 1 -adrenoceptors are G q / 11 -protein-coupled receptors that are activated by the signaling substances adrenaline and noradrenaline . Based on their pharmacological properties, they are divided into four subtypes: α 1A , α 1B , α 1D and “α 1L ”. While the first three subtypes also embody independent receptors at the genomic level , the “α 1L ” adrenoceptor appears to be just a conformational variant of the α 1A subtype.
Occurrence and function
α 1 -adrenoceptors occur in high density in the central nervous system , in the sympathetically innervated tissue, in the salivary glands , especially in the cardiovascular system and in the urogenital tract and in the liver . The stimulation of smooth muscle α 1 -adrenoceptors in blood vessels (subtypes A, B and D) leads to an increase in blood pressure caused by vasoconstriction . A contraction of the organs of the urogenital tract (e.g. prostate and internal sphincter muscle ) is mediated by smooth muscle α 1A / L adrenoceptors and thus leads, for example, to urinary retention . Their role in the central nervous system, on the other hand, is largely unexplored.
pharmacology
α 1 -adrenoceptor agonists : α 1 -adrenoceptor agonists excite sympathetic α 1 -adrenoceptors. They are used systemically or topically (locally) for vasoconstriction:
- Phenylephrine , oxedrine, and the prodrug midodrine, used to treat orthostatic hypotension
- Phenylephrine, oxymetazoline and naphazoline for swelling of the nasal mucosa or conjunctivitis
α 1 -adrenoceptor antagonists (subgroup of alpha blockers ): α 1 -adrenoceptor antagonists inhibit the effects caused by adrenaline and noradrenaline and are therefore used therapeutically:
- Prazosin , doxazosin , terazosin , alfuzosin and urapidil, used to treat hypertensive blood pressure disorders
- Tamsulosin is a selective α 1A / L antagonist and is used specifically for the symptomatic treatment of benign prostatic hyperplasia , as it does not affect the circulation / blood pressure, orthostatic problems or dizziness .
| property | α 1A | α 1B | α 1D | "Α 1L " |
|---|---|---|---|---|
| Agonist | Adrenaline , noradrenaline , phenylephrine | |||
| Selective agonist | A-61603, oxymetazoline | - | Buspirone | A-61603 |
| antagonist | Prazosin , Doxazosin , Terazosin , Alfuzosin , Urapidil , Sertralin , Tamsulosin | |||
| Selective antagonist | 5-methylurapidil , B8805-033, SNAP 5089, RS-17053 | Chloroethylclonidine , L-765314 | BMY 7378, MDL 73005EF | - |
| function | Blood pressure regulation | Blood pressure regulation | Blood pressure regulation (?) | Prostate contraction |
Signal transduction
Through the activation of phospholipase C, α 1 -receptors lead to the formation of the second messenger inositol trisphosphate (IP 3 ) and diacylglycerol (DAG).
IP 3 releases Ca 2+ from the endoplasmic reticulum (ER), which u. a. binds to calmodulin and troponin . DAG influences the activity of other proteins by activating protein kinase C.
literature
- S. Guimarães & D. Moura: Vascular Adrenoceptors: An Update. In: Pharmacol. Rev. 53/2001, pp. 319-356.
- JR Docherty: Subtypes of functional α 1 - and α 2 -adrenoceptors. In: Eur. J. Pharmacol. 361/1998, pp. 1-15.