![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by tealady on November 13, 2004, at 21:31:18
CCK is involved. Actually as with everything, it seems involved in a lot of things
somehow having sufficient sulfates maybe effects thishttp://psychologytoday.psychtests.com/articles/mentalhealth/pd_cckcl.html
Mental Health Articles: Panic Disorder and Agoraphobia
CCK coexists and interacts with other neurotransmitters. It is colocalized and/or interacts with norepinephrine, serotonin, dopamine, GABA, acetylcholine and vasopressinI don't really understand any of this but maybe someone does...
On dopamine autoreceptors...
http://www.acnp.org/g4/GN401000020/CH020.html
"In recent years, it has become apparent that we need to revise our concept of autoreceptors with respect to DA neurons. It has been demonstrated that the peptides cholecystokinin (CCK) and neurotensin are differentially colocalized with DA in subpopulations of midbrain DA neurons. These peptides can be released from the DA neuron and stimulate their specific receptors also located on the DA cell membrane. Thus, we now need to conceptualize DA neurons as possessing not only DA autoreceptors, but also CCK and neurotensin autoreceptors. Moreover, these peptides have the ability to modulate DA autoreceptor function."" Although not proof, these studies suggest that the effect of CCK on DA autoreceptor-mediated inhibition of impulse flow is due to a direct interaction with the DA cell membrane"
"Unsulfated CCK and CCK tetrapeptide are selective CCK-B agonists, and they have been used to explore the question of which receptor subtype is associated with the modulatory effects of CCK on DA autoreceptor function"
Posted by KaraS on November 13, 2004, at 23:23:09
In reply to CCK sulfated/unsulfated..dopamine/CCK autoreceptor, posted by tealady on November 13, 2004, at 21:31:18
>
>
> CCK is involved. Actually as with everything, it seems involved in a lot of things
> somehow having sufficient sulfates maybe effects this
>
> http://psychologytoday.psychtests.com/articles/mentalhealth/pd_cckcl.html
> Mental Health Articles: Panic Disorder and Agoraphobia
> CCK coexists and interacts with other neurotransmitters. It is colocalized and/or interacts with norepinephrine, serotonin, dopamine, GABA, acetylcholine and vasopressin
>
> I don't really understand any of this but maybe someone does...
>
> On dopamine autoreceptors...
> http://www.acnp.org/g4/GN401000020/CH020.html
> "In recent years, it has become apparent that we need to revise our concept of autoreceptors with respect to DA neurons. It has been demonstrated that the peptides cholecystokinin (CCK) and neurotensin are differentially colocalized with DA in subpopulations of midbrain DA neurons. These peptides can be released from the DA neuron and stimulate their specific receptors also located on the DA cell membrane. Thus, we now need to conceptualize DA neurons as possessing not only DA autoreceptors, but also CCK and neurotensin autoreceptors. Moreover, these peptides have the ability to modulate DA autoreceptor function."
>
> " Although not proof, these studies suggest that the effect of CCK on DA autoreceptor-mediated inhibition of impulse flow is due to a direct interaction with the DA cell membrane"
>
> "Unsulfated CCK and CCK tetrapeptide are selective CCK-B agonists, and they have been used to explore the question of which receptor subtype is associated with the modulatory effects of CCK on DA autoreceptor function"
Way over my head here but what I get from this is that sulfation may be a factor influencing certain peptides which effect the DA autoreceptors? I have been recently made aware of three other processes so far that may impact the sensitivity of these autoreceptors - though again they were all a bit out of my range of comprehension. I wonder what your post suggests (if anything) for treatment. Maybe Larry, Ray or JLx can help out here.Thanks for posting this!
Kara
Posted by JLx on November 14, 2004, at 9:40:19
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » tealady, posted by KaraS on November 13, 2004, at 23:23:09
Maybe Larry, Ray or JLx can help out here.
>
> Thanks for posting this!
>
> KaraGood grief, don't include me in their august company! I haven't a clue when it comes to this science stuff. Larry and Ray may as well be speaking Swahili most of the time, afaic. :)
JL
Posted by KaraS on November 14, 2004, at 13:45:27
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » KaraS, posted by JLx on November 14, 2004, at 9:40:19
> Maybe Larry, Ray or JLx can help out here.
> >
> > Thanks for posting this!
> >
> > Kara
>
> Good grief, don't include me in their august company! I haven't a clue when it comes to this science stuff. Larry and Ray may as well be speaking Swahili most of the time, afaic. :)
>
> JL
JL,You're too funny! Your posts sometimes seem like Swahili to me too sometimes.
Kara
Posted by tealady on November 14, 2004, at 15:49:51
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » JLx, posted by KaraS on November 14, 2004, at 13:45:27
> > Maybe Larry, Ray or JLx can help out here.
> > >
> > > Thanks for posting this!
> > >
> > > Kara
> >
> > Good grief, don't include me in their august company! I haven't a clue when it comes to this science stuff. Larry and Ray may as well be speaking Swahili most of the time, afaic. :)
> >
> > JL
>
>
> JL,
>
> You're too funny! Your posts sometimes seem like Swahili to me too sometimes.
>
> KaraWow you both know Swahili?
Posted by raybakes on November 14, 2004, at 16:04:23
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » tealady, posted by KaraS on November 13, 2004, at 23:23:09
>
> Way over my head here but what I get from this is that sulfation may be a factor influencing certain peptides which effect the DA autoreceptors? I have been recently made aware of three other processes so far that may impact the sensitivity of these autoreceptors - though again they were all a bit out of my range of comprehension. I wonder what your post suggests (if anything) for treatment. Maybe Larry, Ray or JLx can help out here.
>
>I only know english, and pretty rubbish at that!
Thanks Jan for that info, I love the work the autistism doctors are doing, and it's the lack of sulphate to activate CCK that some of them think leads to the gut/brain problems seen in autism. MSM is a good supplement to raise sulphate - normal sulphate gives me bowel problems, but I did have an epsom salt solution drip a few years ago and that felt great!
We should generate our own sulphate from the amino acid cysteine, but autoimmune people tend to have a block in the enzyme 'cysteine dioxygenase' causing an accumulation of cysteine and homocysteine.
Ray
Posted by KaraS on November 14, 2004, at 17:27:13
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » KaraS, posted by raybakes on November 14, 2004, at 16:04:23
> We should generate our own sulphate from the amino acid cysteine, but autoimmune people tend to have a block in the enzyme 'cysteine dioxygenase' causing an accumulation of cysteine and homocysteine.
>
> Ray
Ray,I have Hashimoto's which is an autoimmune problem. Does that mean that when I take NAC to prevent neurotoxicity, that it's probably not becoming glutathione and doing what I intended it to - that instead it's just accumulating as cysteine (and horrors) homocysteine???? Yikes!
Kara
Posted by raybakes on November 17, 2004, at 6:28:19
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » raybakes, posted by KaraS on November 14, 2004, at 17:27:13
>
> I have Hashimoto's which is an autoimmune problem. Does that mean that when I take NAC to prevent neurotoxicity, that it's probably not becoming glutathione and doing what I intended it to - that instead it's just accumulating as cysteine (and horrors) homocysteine???? Yikes!
>
> KaraHi Kara,
Sorry to make cysteine sound bad! It really depends on the individual, but cysteine in excess can be toxic. I'm finding that after a week of supplementation, I can't tolerate it - but if I take methyl donors, I don't get those reactions so quickly. My friend with MS collapsed when she took NAC, but I know other people who can take it without any problems.
Ray
Posted by KaraS on November 18, 2004, at 21:00:35
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » KaraS, posted by raybakes on November 17, 2004, at 6:28:19
>
> >
> > I have Hashimoto's which is an autoimmune problem. Does that mean that when I take NAC to prevent neurotoxicity, that it's probably not becoming glutathione and doing what I intended it to - that instead it's just accumulating as cysteine (and horrors) homocysteine???? Yikes!
> >
> > Kara
>
> Hi Kara,
>
> Sorry to make cysteine sound bad! It really depends on the individual, but cysteine in excess can be toxic. I'm finding that after a week of supplementation, I can't tolerate it - but if I take methyl donors, I don't get those reactions so quickly. My friend with MS collapsed when she took NAC, but I know other people who can take it without any problems.
>
> Ray
>
>I have taken 1200 mg a day of Twinlab brand NAC and had no overt problems with it but I wouldn't necessarily know that I was creating too much homocysteine now, would I?
Posted by raybakes on November 21, 2004, at 5:55:12
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » raybakes, posted by KaraS on November 18, 2004, at 21:00:35
>
> I have taken 1200 mg a day of Twinlab brand NAC and had no overt problems with it but I wouldn't necessarily know that I was creating too much homocysteine now, would I?
>It's good you're doing OK with the NAC, I think there are are homocysteine tests available - Over here york labs has one for £75 that I'm thinking about.
Ray
Posted by SLS on November 21, 2004, at 9:24:19
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » tealady, posted by KaraS on November 13, 2004, at 23:23:09
I'm not sure what's going on here. CCK is suppose to increase the sensitivity of DA autoreceptors. Wouldn't this result in a reduction of DA outflow? If this is true, why would someone want to increase their intake of CCK?
Thanks.
- Scott
Posted by raybakes on November 22, 2004, at 6:13:22
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor, posted by SLS on November 21, 2004, at 9:24:19
> I'm not sure what's going on here. CCK is suppose to increase the sensitivity of DA autoreceptors. Wouldn't this result in a reduction of DA outflow? If this is true, why would someone want to increase their intake of CCK?
>
> Thanks.
>
>
> - ScottHi Scott, my interest is not in increasing CCK but how sulphate changes the way it works - tealady's abstracts are quite helpful - what's your understanding?
Ray
Posted by SLS on November 22, 2004, at 11:29:28
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » SLS, posted by raybakes on November 22, 2004, at 6:13:22
> > I'm not sure what's going on here. CCK is suppose to increase the sensitivity of DA autoreceptors. Wouldn't this result in a reduction of DA outflow? If this is true, why would someone want to increase their intake of CCK?
> >
> > Thanks.
> >
> >
> > - Scott
>
> Hi Scott, my interest is not in increasing CCK but how sulphate changes the way it works - tealady's abstracts are quite helpful - what's your understanding?
>
> Ray
>
To tell you the truth, I'm confused about all of this. I wish I had a few of the I.Q. points my depression has ripped away from me. Maybe I would be able to figure this stuff out.What is your interest regarding CCK?
- Scott
Posted by raybakes on November 22, 2004, at 13:29:55
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » raybakes, posted by SLS on November 22, 2004, at 11:29:28
>
> To tell you the truth, I'm confused about all of this. I wish I had a few of the I.Q. points my depression has ripped away from me. Maybe I would be able to figure this stuff out.
>
> What is your interest regarding CCK?
>
>
> - ScottHi Scott, I became interested in CCK because of the work that researchers into autism have been doing with it. My chronic fatigue improves when I try some of the autism spectrum nutritional protocols. When I take MSM as a source of sulphate my gut improves and my mind becomes clearer, so I wondered whether the sulphation of gut and brain CCK might have had anything to do with it?
Hope you can rescue some of your IQ! Since my brain fatigue started I have been able to see patterns within me that I didn't see before, and now, luckily, a lot of energy is coming back - hate being in a fog, but it has changed the way I see the world.
Ray
Posted by SLS on November 22, 2004, at 14:59:23
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » SLS, posted by raybakes on November 22, 2004, at 13:29:55
Hi Ray.
> > What is your interest regarding CCK?
> Hi Scott, I became interested in CCK because of the work that researchers into autism have been doing with it. My chronic fatigue improves when I try some of the autism spectrum nutritional protocols. When I take MSM as a source of sulphate my gut improves and my mind becomes clearer, so I wondered whether the sulphation of gut and brain CCK might have had anything to do with it?
If I'm not mistaken, it is the sulfated form of CCK that has biological activity in the brain where it is colocalized with dopamine.
I'm glad you found something that makes you feel better. You certainly deserve it.
- Scott
Posted by tealady on November 22, 2004, at 17:49:12
In reply to Re: CCK sulfated/unsulfated..dopamine/CCK autoreceptor » raybakes, posted by KaraS on November 18, 2004, at 21:00:35
Hi Kara,
Just occurred to me that estrogen levels play a part in this picture(probably when considered together with hahsimotos and maybe evn previous SSRI use)
..with low estrogen levels maybe causing part of the auto receptor sensitivity problem?...I really get lost, not sure but from clicking on links I posted at the start of this thread and links within these you get to the first one..then following thru
http://www.acnp.org/g4/GN401000056/Default.htmThe ability to visualize CCK mRNA has provided much additional information about the location of CCK cell bodies.
CCK mRNA levels in rat brain are altered by estrogens (medial preoptic area, amygdala, bed nucleus stria terminalis) [97], caffeine (striatum) [143], N-methyl-D-aspartate [NMDA] (striatum) [47], opiates (spinal cord and hypothalamus) [46] and cocaine and benzotript (striatum) [48].
CCK cells are abundant in three sexually dimorphic nuclei in the rat forebrain (the central part of the medial preoptic nucleus, the encapsulated part of the bed nucleus of the stria terminalis, and the posterodorsal part of the media nucleus of the amygdala) [148]. CCK mRNA levels are altered by estrogen in these areas (97).
In the trans-Golgi, three out of four of the tyrosine residues of pro-CCK are sulfated by a specific membrane-bound tyrosine sulfotransferase (109). The sulfation of one of the tyrosine residues (in CCK 8) is important for its biological activity at CCK A receptors. Recent evidence suggests that sulfation of the tyrosines in pro-CCK allows for correct sorting and/or processing of pro-CCK in an endocrine cell in culture (9). This is probably also true for gastrin.
In the trans-Golgi network, sulfated pro-CCK is sorted into secretory granules with other material destined for the regulated secretory pathway.It is important to remember that CCK release requires a stronger stimulus than dopamine release, so it may be more pronounced when animals are stressed or activated.
A large body of evidence indicates that CCK is an excitatory neurotransmitter or neuromodulator, usually activating specific cells directly. In some cases, the action of CCK can be blocked by antagonists of other neurotransmitter systems like DA, 5-HT , GABA or endogenous opiates, suggesting that CCK is releasing other agents which are excitatory or, in some cases, inhibitory (2). CCK excites neurons in the periaqueductal gray (86), dorsal raphe (15), nucleus accumbens (174), hippocampus (18,38,71), ventral medial hypothalamus (15), substantia nigra (130), thalamus (33), and spinal cord (72). It depolarizes oxytocin-containing neurons in the supraoptic nucleus of the hypothalamus (88) and serotonin-containing neurons in the dorsal raphe nucleus.
CCK increases excitatory amino acid release in the hippocampus (100). Most studies indicate that CCK increases GABA release (128) while it decreases dopamine release (54).
97. Micevych PE, Eckersell CB, Holland K, Smith A. Induction of CCK mRNA levels in the limbic-hypothalamic circuit: time course and site-specific effects of estrogen. J Neurobiol 1996;30:465-479.
Micevych PE estrogen enter ito pubmed
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8814910
Regulation of cholecystokinin receptors in the ventromedial nucleus of the hypothalamus: sex steroid hormone effects.In the caudal VMH, in both gonadectomized male and female rats, the levels of CCK-R binding were decreased 24 h after injection of 50 micrograms of estrogen benzoate but were not changed after injection of 300 micrograms of testosterone propionate. We hypothesize that these changes in CCK-R binding in the VMH reflect ligand-induced down-regulation that result from an estrogen-facilitation of stimulated CCK release in the VMH.
------------------------------------------------------------------------------
Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6-hydroxdopamine lesions.Quesada A, Micevych PE.
Department of Neurobiology, Laboratory of Neuroendocrinology, Brain Research Institute, David Geffen School of Medicine UCLA, Los Angeles, California 90095-1763, USA. aquesada@mednet.ucla.edu
The most prominent neurochemical hallmark of Parkinson's disease (PD) is the loss of nigrostriatal dopamine (DA). Animal models of PD have concentrated on depleting DA and therapies have focused on maintaining or restoring DA. Within this context estrogen protects against 6-hydroxdopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions of the nigrostriatal DA pathway. Present studies tested the hypothesis that neuroprotective estrogen actions involve activation of the insulin-like growth factor-1 (IGF-1) system. Ovariectomized rats were treated with either a single subcutaneous injection of 17beta-estradiol benzoate or centrally or peripherally IGF-1. All rats were infused unilaterally with 6-OHDA into the medial forebrain bundle (MFB) to lesion the nigrostriatal DA pathway. Tyrosine hydroxylase (TH) immunocytochemistry confirmed that rats injected with 6-OHDA had a massive loss of TH immunoreactivity in both the ipsilateral substantia nigra compacta (60% loss) and the striatum (>95% loss) compared to the contralateral side. Loss of TH immunoreactivity was correlated with loss of asymmetric forelimb movements, a behavioral assay for motor deficits. Pretreatment with estrogen or IGF-1 significantly prevented 6-OHDA-induced loss of substantia nigra compacta neurons (20% loss) and TH immunoreactivity in DA fibers in the striatum (<20% loss) and prevented the loss of asymmetric forelimb use. Blockage of IGF-1 receptors by intracerebroventricular JB-1, an IGF-1 receptor antagonist, attenuated both estrogen and IGF-1 neuroprotection of nigrostriatal DA neurons and motor behavior. These findings suggest that IGF-1 and estrogen acting through the IGF-1 system may be critical for neuroprotective effects of estrogen on nigrostriatal DA neurons in this model of PD. Copyright 2003 Wiley-Liss, Inc.
PMID: 14689453 [PubMed - indexed for MEDLINE]
-------------------------------------------------------------------------Just something else to maybe consider <g>
Jan
This is the end of the thread.
Psycho-Babble Alternative | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.