Spring Break
Rethinking chemical signals in bird brains
Issue date: 3/13/08
One of these dopamine-like molecules is norepinephrine, which binds to alpha-2-adrenergic receptors. "There are high densities of certain noradrenergic receptor subtypes in these brain nuclei involved in song control," Ball said.
There are, however, many reasons to believe that dopamine could also bind to norepinephrine receptors. For one, dopamine and norepinephrine are chemical siblings.
Indeed, dopamine and norepinephrine are only one degree removed in the chain of neurotransmitter synthesis that takes place in neurons' cell bodies. There, enzymes turn dopamine into norepinephrine by lopping off a hydroxyl group, which consists of an oxygen and a hydrogen, and replacing it with a simple carbon group.
First, the team needed to answer a few basic questions: Does dopamine bind at all to alpha-2-adrenergic receptors? If so, how well does it bind? To figure this out, the team injected zebra finches with a radioactive alpha-2-adrenergic receptor antagonist.
In technical parlance, a receptor antagonist is a substance that binds to a particular receptor without evoking any biological response. Because it was radioactive, the injected antagonist allowed the team to pinpoint exactly where alpha-2-adrenergic receptors were located in the finch's song areas.
But it also let the researchers test their dopamine-binding hypothesis.
The key idea here is that all binding is competitive. Hundreds of molecules, each with its own affinity for a particular receptor, vie for the privilege to bind to a single receptor. Thus, if dopamine does indeed interact with alpha-2-adrenergic receptors, it should displace the radioactive antagonist.
That's exactly what the researchers observed. Dopamine, they found, has an affinity for the alpha-2-adrenergic receptor - albeit between ten and 28 times lower than norepinephrine, the receptor's "classical" binding partner.
"This means that a neurotransmitter system whose activity and release is regulated in a manner quite distinct from norepinephrine can also act upon the song system via adrenergic receptors," Ball said.
Nonetheless, the researchers cautioned that the physiological significance of dopamine's binding to this novel class of receptor is uncertain.
Interestingly, the team's results do seem to extend to non-bird brains (species-wise, that is). "We've conducted studies on this phenomenon in rats and on a cell line that expresses the human adrenergic receptor and found similar results," Ball said. "So, we do think this finding applies to mammals, including humans."
There are, however, many reasons to believe that dopamine could also bind to norepinephrine receptors. For one, dopamine and norepinephrine are chemical siblings.
Indeed, dopamine and norepinephrine are only one degree removed in the chain of neurotransmitter synthesis that takes place in neurons' cell bodies. There, enzymes turn dopamine into norepinephrine by lopping off a hydroxyl group, which consists of an oxygen and a hydrogen, and replacing it with a simple carbon group.
First, the team needed to answer a few basic questions: Does dopamine bind at all to alpha-2-adrenergic receptors? If so, how well does it bind? To figure this out, the team injected zebra finches with a radioactive alpha-2-adrenergic receptor antagonist.
In technical parlance, a receptor antagonist is a substance that binds to a particular receptor without evoking any biological response. Because it was radioactive, the injected antagonist allowed the team to pinpoint exactly where alpha-2-adrenergic receptors were located in the finch's song areas.
But it also let the researchers test their dopamine-binding hypothesis.
The key idea here is that all binding is competitive. Hundreds of molecules, each with its own affinity for a particular receptor, vie for the privilege to bind to a single receptor. Thus, if dopamine does indeed interact with alpha-2-adrenergic receptors, it should displace the radioactive antagonist.
That's exactly what the researchers observed. Dopamine, they found, has an affinity for the alpha-2-adrenergic receptor - albeit between ten and 28 times lower than norepinephrine, the receptor's "classical" binding partner.
"This means that a neurotransmitter system whose activity and release is regulated in a manner quite distinct from norepinephrine can also act upon the song system via adrenergic receptors," Ball said.
Nonetheless, the researchers cautioned that the physiological significance of dopamine's binding to this novel class of receptor is uncertain.
Interestingly, the team's results do seem to extend to non-bird brains (species-wise, that is). "We've conducted studies on this phenomenon in rats and on a cell line that expresses the human adrenergic receptor and found similar results," Ball said. "So, we do think this finding applies to mammals, including humans."
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