As written before , cAMP is crucial for energy metabolism , heart function/contractility, to maintain normal blood pressure and as well for steroidogenesis. Without cAMP, many immunological reactions would not occur, we would be stricken with chronic asthma and allergies, and would feel utterly castrated.
Now a connection has been made to determine the potency of 5-HT1A mediated INHIBITION of cAMP, and while more research needs to be done, it is profoundly clear that the receptor 5-HT1A, partially from somatodendritic receptors - but mostly from post-synaptic receptors, is able to almost completely abolish the forskolin stimulated cAMP.
WHY is this bad?
For the reasons above, and it makes sense that we want cAMP around - not too much, but certainly, we do not want it abolished or directly inhibited. Given cAMP's established role in sex hormone production, it is significant to declare that this is a vital path we must address in order to treat PSSD. Especially in those presenting with hypothyrodism after SSRI use or AD therapy.
The study below draws serious implications for how we address PSSD, and our status on the use of 5-HT1A agonists may need to be re-evaluated.
Now a connection has been made to determine the potency of 5-HT1A mediated INHIBITION of cAMP, and while more research needs to be done, it is profoundly clear that the receptor 5-HT1A, partially from somatodendritic receptors - but mostly from post-synaptic receptors, is able to almost completely abolish the forskolin stimulated cAMP.
WHY is this bad?
For the reasons above, and it makes sense that we want cAMP around - not too much, but certainly, we do not want it abolished or directly inhibited. Given cAMP's established role in sex hormone production, it is significant to declare that this is a vital path we must address in order to treat PSSD. Especially in those presenting with hypothyrodism after SSRI use or AD therapy.
The study below draws serious implications for how we address PSSD, and our status on the use of 5-HT1A agonists may need to be re-evaluated.
Biochem Pharmacol. 1993 Jan 26;45(2):375-83.
Activity of serotonin (5-HT) receptor agonists, partial agonists and antagonists at cloned human 5-HT1A receptors that are negatively coupled to adenylate cyclase in permanently transfected HeLa cells.
Pauwels PJ1, Van Gompel P, Leysen JE.
Author information
Abstract
The activity of serotonin (5-HT) receptor agonists, partial agonists and antagonists, and various other neurotransmitter receptor antagonists at human 5-HT1A receptors that are negatively coupled to adenylate cyclase in permanently transfected HeLa cells was investigated. 5-HT1A receptor-mediated inhibition of adenylate cyclase was studied by measuring inhibition of cAMP accumulation, induced by forskolin. At 100 microM forskolin produced a 100-fold increase in cAMP formation: 5-HT concentration dependently inhibited the cAMP formation; maximal inhibition was attained at 1 microM 5-HT and represented 90% of the stimulated cAMP formation. Full inhibition was observed with 5-HT1A receptor agonists: N,N-dipropyl-8-hydroxy-2-aminotetralin (8-OH-DPAT) and flesinoxan, and non-selective 5-HT receptor agonists: d-lysergic acid diethylamide (d-LSD), RU 24,969, bufotenine, methysergide and tryptamine. The rank order of potency of the compounds for inhibiting the cAMP formation corresponded to the rank order of the binding affinities of the drugs for the 5-HT1A receptor. Partial inhibition was obtained with submicromolar concentrations of buspirone, spiroxatrine and ipsapirone. A slight inhibition was observed with 1 microM 5-HT receptor agonist CP 93129 and 1 microM 5-HT receptor antagonists mesulergine and BW-501. No inhibition was found with: the 5-HT receptor agonists quipazine, sumatriptan and 1-(2,5-dimethoxy-4-methylphenyl)-2- aminopropane (DOM); the 5-HT receptor antagonist ICS-205,930; and other neurotransmitter receptor antagonists such as pindolol, CGP 20712-A, prazosin, sulpiride and pyrilamine. Spiperone and pindolol fully antagonized the agonist-mediated inhibition of forskolin-stimulated cAMP formation. Partial inhibition of the agonist-mediated inhibition of forskolin-stimulated cAMP formation was apparent with 1 microM ocaperidone and 1 microM ipsapirone. It can be concluded that HeLa cells, permanently expressing human 5-HT1A receptors, are a valid cellular system for studying the negative coupling of 5-HT1A receptors to adenylate cyclase and the action of compounds thereupon.
PMID: 8382063 [PubMed - indexed for MEDLINE]
