Cholera leads to the constant activation of adenylyl cyclase, and so does pertussis (by different inhibition mechanisms). I understand how cholera leads to the constant opening of Cl channels, leading to diarrhea since water follows ions out, but how does pertussis lead to whooping cough in this regard?

which one is the best and why?

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The alpha (α) -1 adrenergic receptor antagonists (also called alpha-blockers) are a family of agents that bind to and inhibit type 1 alpha-adrenergic receptors and thus inhibit smooth muscle contraction. Appart from their use in neuro-psychiatry, their major uses are for hypertension and for symptomatic benign prostatic hypertrophy. Their use in therapy of hypertension is based on the inhibition of vascular resistance in arterioles from alpha-adrenergic blockade, which results in an increase in venous capacitance and lowering of blood pressure.

Alpha1-adrenergic receptors are engaged in a range of autonomic, neuroendocrine and behavioral functions. These comprise motor functions, attention and vigilance, fear and anxiety, reinforcement, sensory gating, learning, sexual behavior, and regulation of blood pressure and of both the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal systems (HPA and HPG Axis).Alpha1-adrenergic receptors also regulate mesocorticolimbic dopamine systems and multiple reactions to addictive drugs. They are located primarily in the pre-synaptic regions (unmyelinated axons and axon terminals) of the mesocorticolimbic system, thereby regulating neurotransmission in this area, as well as drug generated modifications in extracellular dopamine concentration and locomotor activation.

Here I quote part of the article "Alpha1-Adrenergic Receptor Antagonists Use in Treatment and Prevention of Psychiatric Disorders", by Abhishek Wadhawan et al, 2015.

"Potential Role of Alpha1-Adrenergic Antagonists in Treating Mood Disorders

Prazosin has been shown to improve anhedonia, which is a part of the depressive symptoms in hypertensive patients, but prazosin or other A1As have not been formally studied in other mood disorders. It is well known that depressive states are related to hypothalamic-pituitary-adrenocortical (HPA) system activation. HPA activation is associated with psychomotor agitation and anxiety in both major depressive disorder (MDD) and bipolar disorder (BD). Increased arousal is an exceedingly prominent feature of activated depressions, whether they are characterized as mixed states [with features of both melancolia and atypcal-anergic depression] or as agitated depression. Similarly, sympatho-adreno-medullary function is also augmented in a manner that correlates with the severity of anxiety and agitation in MDD or BD depressed patients without manic symptoms, as well as in mixed mania [neg

I'm aware of the role they play in pharmacotherapy, but their activation confers sedative/inhibitory effects, and norepinephrine is consistently involved in excitatory/CNS stimulant processes. What's the deal here? Are there any situations in which alpha-2 stimulation dominates? Do they just serve to counteract excessive CNS stimulation that might occur?

What I find incredibly interesting about alpha 2 adrenergic receptors is that presynaptically, they inhibit norepinephrine's release through the binding of norepinephrine itself.

I feel like the existence of these receptors themselves could explain much of the diversity within several disorders of the adrenergic system such as ADHD. Could poor function of said receptors be a reason why many people with ADHD experience emotions to a much more intense degree? Could just a minute NE deficiency lead to significantly altered function of the a2 receptors

When activated, how long do they stay activated for and what is the magnitude of their inhibition relative to the amount of NE required to activate a given receptor?

And finally the title question, Is it possible that stimulation of the a2 receptors persisting after reaching peak NE content from amphetamines causes an exacerbation of the comedown effects resulting from an imbalance between external NE and NE bound to the a2 receptors?

I've been looking into them and many studies such as this mention an increased presynaptic sensitivity/responsiveness and decreased postsynaptic sensitivity/responsiveness in certain mental illnesses like panic disorder and a presynaptic subsensitivity in schizophrenia.

I've read that presynaptically alpha 2 receptors have norepinephrine bind to them to prevent its own release while postsynaptically norepinephrine binds to produce stimulating effects, but the wording on some of these studies can be confusing.

This study mentions the existence of postsynaptic inhibitory alpha 2 adrenoceptors which seems to contradict what I initially thought their function.

Which leads to my next question, this study implies that in ADHD there's elevated levels of NE at the postsynaptic a2A receptors in the PFC. How exactly would people with ADHD have elevated postsynaptic a2A binding without an elevated presynaptic a2A binding to match? Most of the studies I've read almost make it seem like presynaptic a2 receptors are almost entirely responsible for binding at postsynaptic a2 receptors through their inhibition or lack thereof.

Lastly this study, along with this one seem to clarify that only the postsynaptic a2A receptors have stimulatory effects while all the the other a2 receptor subtypes, pre or postsynaptic, have inhibitory effects.

I am posting here because I do want an explanation, but I'd like it said in terms any average student would understand, which I don't think ELI5 would be able to provide this time around.

Edit: Thanks to all who have answered my question so far. I'm a nursing student taking Med-Surg (in my second semester out of four to take my NCLEX), which means for now a lot of the material is introductory, but so far I am understanding the material well decently.

Hi everyone,

I'm having trouble understanding alpha-adrenergic receptors:

I know that agonizing alpha-1 will constrict smooth muscle and antagonizing alpha-1 will dilate smooth muscle, hence the use of a *-zosin for combined HTN and BPH

Does alpha-2 do the same thing? Why is it that AGONIZING central alpha-2 receptors via clonidine causes a decrease in blood pressure? What do peripheral alpha2 receptors do?

EDIT: just answered my own question.

1. Alpha 2 is not found peripherally, only centrally
2. Agonizing alpha2 leads to transient hypertension followed by sustained hypotension.

I would really appreciate if anyone could get me this article:

ttp://www.ncbi.nlm.nih.gov/pubmed/9328010 AU = Arnsten AF, Steere JC, Jentsch DJ, Li BM. Adv Pharmacol. 1998;42:764-7.

Thanks in advance

https://preview.redd.it/jgj8b1mvhc981.jpg?width=500&format=pjpg&auto=webp&s=3373ae614d44e0e80b72d8b2c0bf1ae49814af98

Note about Ki

>Binding Affinity – The Measure of Separation
>
>Scientists test how well drugs and chemicals bind to receptors by measuring their binding affinity, designated by the symbol Ki. Binding affinity is one kind of dissociation constant. This means that the higher the number, the more likely the substance is to separate from the receptor. Conversely, low binding affinity values mean the substance binds more strongly and is less likely to dissociate from the receptor. These binding affinities are measured in nanomoles (nM). ^([1])

Key

Source

• Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens [Jan 2011]
• Watching this ELI5: 2-Minute Neuroscience: Psilocybin | Neuroscientifically Challenged [May 2020] video which includes the following comment (from the video description):

>Psilocin also interacts with other targets, like other serotonin receptor subtypes, some subtypes of dopamine, histamine, and adrenergic receptors, and the serotonin transporter;

• resulted in finding this [psilocin table](https://images.squarespace-cdn.

r/microdosing Disclaimer

[Updated: Jan 3, 2021 - EDIT]

Psilocybin mushrooms/truffles

• Psilocybin is a prodrug which after ingestion is converted to psychoactive psilocin (4-OH-DMT) by the process of dephosphorylation ^([1])
• Prodrugs are generally not pharmacologically active until they are ingested and metabolised by the body which can lead to higher bioavailability.

>Without the phosphate group, psilocin becomes more lipid soluble than psilocybin, making it metabolically available in the body and more easily absorbed in the intestines.
>
>At this point, psilocin is distributed all over the body via the bloodstream. Being lipid soluble allows psilocin to cross the blood-brain barrier and elicit its effects.^([2])

• In the case of psilocybin it is unclear if this leads to any psychoactive effects, as the above quoted section implies that psilocybin could be partially lipid soluble.
• Both psilocybin and psilocin have some binding affinity to the various serotonin receptors. See 🔢 Binding affinities for psilocybin and psilocin at 5-HT receptors. This also suggests that psilocybin may be somewhat pharmacologically active while not necessarily psychoactive.
• EDIT: Psilocin also binds to a couple of alpha-1 adrenergic receptors, one dopamine receptor (out of five) and one histamine receptor as shown in this table, but (excluding histamine) with higher Ki values than LSD^([3]) implying that there are minimal effects. Although psilocin could have an antihistamine effect.
• As well as psilocybin and psilocin, mushrooms/truffles also contain other tryptamine compounds such as norpsilocin, aeruginascin, baeocystin, [norbaeocystin](https://psychedelicreview.c

Which a-adrenergic receptors are involved in regulating K+ balance? Is there a reason why which beta receptors are specified but not alpha?

https://preview.redd.it/5r8avktqc6171.png?width=503&format=png&auto=webp&s=7ccdb66c47db83d0134df3eef9e24e3e268f5f6b

Hello smart and kind people!

Page 241 of First Aid 2021 says β3 receptors "Increases thermogenesis in skeletal muscle". However on Page 240, in the chart " Tissue distribution of adrenergic receptors " at the bottom of the page, it says that skeletal muscle do not have any β3 receptors.

How can β3 receptors "Increases thermogenesis in skeletal muscle" when they are not present on skeletal muscle?

Thanks!

I am having trouble remembering what each receptor will cause an effector organ to do. What are some tricks to learn this other than brute memorization?

I don't get the "logic" behind it. Is it coincidental? Would release of vasopressin with alpha-1 activity be a bad thing?

I know both can do vasoconstriction, but ADH also causes solute-free water retention—something that alpha-1 receptors can't mediate.

Thank you!

I know they give beta blockers or a2 agonists for anxiety sometimes as they reduce activity of noradrenaline at adrenergic receptors in various ways.

I also know there is no single consensus on the pathophysiology of anxiety, as multiple systems can be involved.

So besides their adrenergic activity, do beta blockers have any sort of effect on the GABA receptors/signaling? Even if its indirect? And by the same virtue, does the adrenergic system interact with the GABA system at all? Does adrenergic activity reduce GABA signaling?

The only information I could find about them is that "the presynaptic alpha-2a receptor inhibits further norepinephrine release". Ok, but what about the post-synaptic alpha-2a and if there is, central a1, and central beta receptors?

I was looking for gene mutations associated with less sleep, as I seem to be very tolerant of not sleeping very much.

I found I am homozygous G:G for Rs121912617, so I theoretically need roughly 2 (or slightly more) hours less sleep than others.

I find I am able to thrive on even less sleep, and do fine provided I stay over 4 hours.

I was googling today and found this article: A Rare Mutation of β1-Adrenergic Receptor Affects Sleep/Wake Behaviors (https://www.sciencedirect.com/science/article/abs/pii/S089662731930652X?via%3Dihub#:~:text=We%20have%20identified%20a%20mutation,mutation%20demonstrated%20short%20sleep%20behavior.)

I was hoping some intrepid dataminer out there knew which SNP was associated with this mutation, and could help me figure out how to dig through my 23andme to figure out if I've got it.

Thanks

The alpha (α) -1 adrenergic receptor antagonists (also called alpha-blockers) are a family of agents that bind to and inhibit type 1 alpha-adrenergic receptors and thus inhibit smooth muscle contraction. Appart from their use in neuro-psychiatry, their major uses are for hypertension and for symptomatic benign prostatic hypertrophy. Their use in therapy of hypertension is based on the inhibition of vascular resistance in arterioles from alpha-adrenergic blockade, which results in an increase in venous capacitance and lowering of blood pressure.

Alpha1-adrenergic receptors are engaged in a range of autonomic, neuroendocrine and behavioral functions. These comprise motor functions, attention and vigilance, fear and anxiety, reinforcement, sensory gating, learning, sexual behavior, and regulation of blood pressure and of both the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal systems (HPA and HPG Axis).Alpha1-adrenergic receptors also regulate mesocorticolimbic dopamine systems and multiple reactions to addictive drugs. They are located primarily in the pre-synaptic regions (unmyelinated axons and axon terminals) of the mesocorticolimbic system, thereby regulating neurotransmission in this area, as well as drug generated modifications in extracellular dopamine concentration and locomotor activation.

Here I quote part of the article "Alpha1-Adrenergic Receptor Antagonists Use in Treatment and Prevention of Psychiatric Disorders", by Abhishek Wadhawan et al, 2015.

"Potential Role of Alpha1-Adrenergic Antagonists in Treating Mood Disorders

Prazosin has been shown to improve anhedonia, which is a part of the depressive symptoms in hypertensive patients, but prazosin or other A1As have not been formally studied in other mood disorders. It is well known that depressive states are related to hypothalamic-pituitary-adrenocortical (HPA) system activation. HPA activation is associated with psychomotor agitation and anxiety in both major depressive disorder (MDD) and bipolar disorder (BD). Increased arousal is an exceedingly prominent feature of activated depressions, whether they are characterized as mixed states [with features of both melancolia and atypcal-anergic depression] or as agitated depression. Similarly, sympatho-adreno-medullary function is also augmented in a manner that correlates with the severity of anxiety and agitation in MDD or BD depressed patients without manic symptoms, as well as in mixed mania [neg