Abstract
During postnatal development, alpha-2 adrenergic receptors (A2AR) change in both density and distribution. In forebrain, receptor density increases about 4-fold over neonatal levels, reaching adult levels before postnatal day (P) 28, whereas in hindbrain, including cerebellum, there is a decrease in overall receptor density. We examined the coupling of A2AR to G proteins using agonist-stimulated [35S]GTPγS binding as a functional assay. In forebrain the A2AR agonist-stimulated [35S]GTPγS binding increases rapidly after P7, reaching its highest levels at P21 and then declining slightly to adult levels. This binding increases more slowly than receptor number, suggesting that the appearance of G proteins, rather than the A2AR, determines the developmental appearance of functional A2AR-G protein interactions in forebrain. Basal [35S]GTPγS binding and [35S]GTPγS binding stimulated by other neurotransmitter receptor systems (GABA-B,mu opiate, and muscarinic) increase with a time course similar to A2AR-stimulated [35S]GTPγS binding. In contrast, in hindbrain, A2AR-stimulated [35S]GTPγS binding decreases during postnatal development in parallel with the decrease in A2AR levels, whereas [35S]GTPγS binding stimulated by other neurotransmitter receptor systems increases in parallel with basal [35S]GTPγS binding. Functional receptor-G protein coupling in hindbrain appears to be dependent on the developmental appearance of G proteins for most neurotransmitter systems. However, for A2AR the decrease in receptor density is the overriding factor. These studies 1) demonstrate the functional measurement of A2AR-G protein coupling in native tissue for the first time, 2) demonstrate that A2AR are coupled to G proteins throughout postnatal development, and 3) describe developmental increases and decreases in functional A2AR in brain.
Footnotes
-
Send reprint requests to: L. Charles Murrin, Ph.D., Department of Pharmacology, University of Nebraska Medical Center, 600 South 42nd St., Omaha, NE 68198-6260. Email: cmurrin{at}unmc.edu
-
↵1 This work was supported by National Institutes of Health Grant NS 38201. Part of this work has been reported previously in abstract form (Happe et al., 1998).
- Abbreviations:
- A2AR
- alpha-2 adrenergic receptors
- CNS
- central nervous system
- carbachol
- carbamyl choline
- P
- postnatal day
- Received June 30, 1998.
- Accepted October 7, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|