| First Author | Hein L | Year | 1999 |
| Journal | Nature | Volume | 402 |
| Issue | 6758 | Pages | 181-4 |
| PubMed ID | 10647009 | Mgi Jnum | J:58591 |
| Mgi Id | MGI:1349253 | Doi | 10.1038/46040 |
| Citation | Hein L, et al. (1999) Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature 402(6758):181-4 |
| abstractText | The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Alpha2-adrenergic receptors are known to have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system; however, the individual roles of the three highly homologous alpha2-adrenergic-receptor subtypes (alpha2A, alpha2B, alpha2C) in this process are not known. We have now studied neurotransmitter release in mice in which the genes encoding the three alpha2-adrenergic-receptor subtypes were disrupted. Here we show that both the alpha2A- and alpha2C-subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. Alpha2A-adrenergic receptors inhibit transmitter release at high stimulation frequencies, whereas the alpha2C-subtype modulates neurotransmission at lower levels of nerve activity. Both low- and high-frequency regulation seem to be physiologically important, as mice lacking both alpha2A- and alpha2C-receptor subtypes have elevated plasma noradrenaline concentrations and develop cardiac hypertrophy with decreased left ventricular contractility by four months of age. |
