Yet Another Bulletin Board

Welcome, Guest. Please Login or Register.
Mar 26th, 2019, 2:23am

Home Home Help Help Search Search Members Members Member Map Member Map Login Login Register Register
Clusterheadaches.com Message Board Serotonin receptor puzzle


   Clusterheadaches.com Message Board
   New Message Board Archives
   Medications, Treatments, Therapies 2003
(Moderator: DJ)
   Serotonin receptor puzzle
« Previous topic | Next topic »
Pages: 1  Reply Reply Notify of replies Notify of replies Send Topic Send Topic Print Print
   Author  Topic: Serotonin receptor puzzle  (Read 2590 times)
CJohnson
New Board Old Timer
USA 
****




Cannot kill the family, Battery is found in me

   
Email

Gender: male
Posts: 442
Serotonin receptor puzzle
« on: Dec 22nd, 2003, 12:10pm »
Quote Quote Modify Modify

 Hmmmm.... Maybe we have plenty of serotonin in the right place at the right time. Could be one of the problems is that sometimes when the serotonin gets to where it is supposed to go, the receptor doesn't do what its supposed to do.
 
Abnormal 5-HT1D receptor function in cluster headache: a neuroendocrine study with sumatriptan
 
"The purpose of this study was to assess the sensitivity of 5-HT1D receptors in patients with episodic cluster headache using sumatriptan as a pharmacological probe. The drug, a selective 5-HT1B/1D agonist, stimulates the secretion of growth hormone and inhibits the release of prolactin, adrenocorticotropic hormone (ACTH) and cortisol. These effects may be used to explore the function of serotonergic systems in vivo. We administered subcutaneous sumatriptan and placebo to 20 patients with cluster headache (10 in the active phase and 10 in the remission period) and to 12 controls. The sumatriptan-induced increase of growth hormone concentrations was significantly (P < 0.05) blunted in patients with active cluster headache. Prolactin and ACTH responses to the drug were significantly (P < 0.05) reduced in patients with cluster headache, both in the active and in the remission period. Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are altered in patients with episodic cluster headache."
 
http://www.blackwell-synergy.com/links/doi/10.1046/j.1468-2982.2003.0054 5.x/abs/;jsessionid=ckmKpL6aPkG-
 
PFDANs
-Curtis
IP Logged

Through water and fire. From the lowest dungeon to the highest peak, I fought the Beast. Until at last, I threw down my enemy and smote his ruin upon the mountainside.
floridian
Guest

Email

Re: Serotonin receptor puzzle
« Reply #1 on: Dec 22nd, 2003, 4:31pm »
Quote Quote Modify Modify Remove Remove

It's easy to boost serotonin by eating precursors (tryptophan, 5htp), or to boost serotonin by reducing its destruction (SSRIs, MAOIs, etc).  But if the "lock" is broken, more "keys" may not help.  
 
Another take on the experiment you posted is that the receptors are fine, but something else is blocking the serotonin message from getting through.  Maybe the sumatriptan binds to the nerve cell, the inside of the cell says "aha, 5-ht1d!!"  but doesn't fully respond due to some other chemical inhibitor.  After all, the triptans do help with the pain of cluster headaches, so something is working.  
 
The receptor defect idea fits with other research on clusterheads having disturbed cell membranes. Phosphatidylcholine builds up, but free choline is low (could be impaired phospholipase enzymes).  This is linked to inositol compounds that act as a secondary messenger for serotonin - inositol has been used to treat depression and panic - it is as effective (or more effective) than SSRIs, even though it doesn't directly affect serotonin levels.  
 
Importantly, inositol seems to reverse the desensitization of serotonin receptors (see second quote below).
 
 
Quote:
Cephalalgia. 1986 Sep;6(3):147-53.
 
    Abnormal membrane composition and membrane-dependent transduction mechanisms in cluster headache.   de Belleroche J, Kilfeather S, Das I, Rose FC.
 
    Previous studies have indicated that membrane structure and function may be abnormal in cluster headache. This has been further investigated by analysis of membrane phosphatidylcholine, total phospholipids, and cholesterol in erythrocytes and by assay of receptor-mediated transduction. The stimulation of lymphocyte adenylate cyclase with isoprenaline and prostacyclin was used as the test system. A significant increase in the ratio of membrane phosphatidylcholine to cholesterol without change in cholesterol was found in cluster headache patients as compared with control subjects. This indicated a reduced turnover of phosphatidylcholine, since erythrocyte choline is significantly reduced in this condition. Abnormal membrane function was also indicated from the significant depression of high-affinity prostaglandin receptor stimulation of lymphocyte adenylate cyclase and the similar trend in the beta-adrenoceptor response. Since no change in agonist affinity and beta-adrenoceptor density occurred, this depression indicates a generalized defect in coupling of receptors to adenylate cyclase. It is hypothesized that the impaired function that would result might contribute to the aetiology of cluster headache.

 
Quote:
 
 ... inositol is reported to reverse desensitization of serotonin receptors ...  
 
Eur Neuropsychopharmacol. 1997 May;7(2):147-55.     Controlled trials of inositol in psychiatry.
 
    Levine J.  Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
« Last Edit: Dec 22nd, 2003, 4:48pm by floridian » IP Logged
CJohnson
New Board Old Timer
USA 
****




Cannot kill the family, Battery is found in me

   
Email

Gender: male
Posts: 442
Re: Serotonin receptor puzzle
« Reply #2 on: Dec 23rd, 2003, 11:14am »
Quote Quote Modify Modify

 Indeed, sumatriptan does the job. Why, I wonder, should sumatriptan block the release of CGRP and terminate the activity of the trigeminal nerve when it binds to the 5ht1d receptor, yet does not increase growth hormone concentrations as it should? The secondary messenger idea is an intriguing one.
 
 The following exerpt describes how lithium acts on the phosphoinositide cycle to have a meaningful and prophylactic effect on the circadean rhythm of cluster sufferers by means of secondary messengers.
 
 "As discussed above (see discussion of biologic clocks), the hypothalamic pacemaker is serotonergically innervated, and perhaps it is on this basis that lithium has prominent effects on circadian rhythms, acting to slow and alter them (Kafka et al, 1982; Kripke and Wyborney, 1980).  The molecular site of action for lithium is currently believed to be at a second messenger system in the CNS (Worley et al, 1987).  The polyphosphoinositides are a group of membrane phospholipids that, when activated, release two products both of which act as second messengers:  Diacylglocerol and inositol triphosphate.  This second messenger system is particularly abundant in brain and modulates many aspects of synaptic transmission.  Lithium's actions on the phosphoinositide cycle may underlie its therapeutic actions."  
 
PFDANs
-Curtis
IP Logged

Through water and fire. From the lowest dungeon to the highest peak, I fought the Beast. Until at last, I threw down my enemy and smote his ruin upon the mountainside.
CJohnson
New Board Old Timer
USA 
****




Cannot kill the family, Battery is found in me

   
Email

Gender: male
Posts: 442
Re: Serotonin receptor puzzle
« Reply #3 on: Dec 29th, 2003, 1:41pm »
Quote Quote Modify Modify

Brain Res. 2002 Oct 4;951(2):280-92.  
 
Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase.
 
*Note: from Floridian's post that abnormal membrane function was indicated in cluster headache by significantly reduced stimulation of adenylyl cyclase
 
Xu Z, Seidler FJ, Cousins MM, Slikker W Jr, Slotkin TA.
 
Department of Pharmacology and Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710, USA.
 
Nicotine is a neuroteratogen that targets synaptic function during critical developmental stages and recent studies indicate that CNS vulnerability extends into adolescence, the age at which smoking typically commences. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined 5HT receptors and related cell signaling during nicotine administration (PN45) and in the post-treatment period (PN50, 60, 75). Adolescent nicotine decreased 5HT(2) receptor binding in brain regions containing 5HT projections (hippocampus and cerebral cortex), with selectivity for females in the cerebral cortex; regions containing 5HT cell bodies showed either an increase (midbrain in males) or no change (brainstem). In contrast, there were no significant changes in 5HT(1A) receptors; however, the ability of the receptors to signal through adenylyl cyclase (AC) showed a switch from stimulatory to inhibitory effects in females during the post-treatment period. There were also transient alterations in AC responses to beta-adrenergic receptor stimulation, as well as pronounced induction of the AC response to the non-receptor-mediated stimulant, forskolin. Our results indicate that adolescent nicotine exposure alters the concentrations and functions of postsynaptic 5HT receptors in a manner commensurate with impaired 5HT synaptic function. The direction of change, emergence of defects after the cessation of nicotine administration, and sex-preference for effects in females, all support a relationship of impaired 5HT function to the higher incidence of depression seen in adolescent smokers.
 
PMID: 12270507 [PubMed - indexed for MEDLINE]  
 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed &list_uids=12270507&dopt=Abstract
 
PFDANs
-Curtis
IP Logged

Through water and fire. From the lowest dungeon to the highest peak, I fought the Beast. Until at last, I threw down my enemy and smote his ruin upon the mountainside.
Pages: 1  Reply Reply Notify of replies Notify of replies Send Topic Send Topic Print Print

« Previous topic | Next topic »


Clusterheadaches.com Message Board » Powered by YaBB 1 Gold - SP 1.3.1!
YaBB 2000-2003. All Rights Reserved.


1998-2010 Web Vision Enterprises All rights reserved. All information on this site is protected by international copyright laws. You may not re-distribute any information from this site without written permission from Web Vision Enterprises and the webmaster of this site. Violators will be prosecuted.
You may view our privacy policy and financial disclosure statement here

test rss