Editing Chemoreceptor trigger zone (section)

==Communication==
The vomiting center of the brain refers to the groups of loosely organized neurons in the medulla that include the CTZ within the area postrema and the [[nucleus tractus solitarii]].<ref name="Vomiting center"/> 
One of the ways the chemoreceptor trigger zone implements its effects on the vomiting center is by activation of the opioid [[mu receptors]] and [[delta receptors]].<ref name="Porreca">{{cite journal|last1=Porreca|first1=Frank|last2=Ossipov|first2=Michael H.|title=Nausea and Vomiting Side Effects with Opioid Analgesics during Treatment of Chronic Pain: Mechanisms, Implications, and Management Options|journal=Pain Medicine|date=May 2009|volume=10|issue=4|pages=654–662|doi=10.1111/j.1526-4637.2009.00583.x|pmid=19302436|doi-access=free}}</ref> The activation of these opioid receptors in the CTZ are especially important for patients who take opioid based pain medications on a regular basis. However, opioids do not play a role in communication to the vomiting center of the brain, they only induce communication.<ref name="Porreca"/> Dopamine and serotonin have been found to play the biggest role in communication from the CTZ to the remainder of the vomiting center, as well as histamine.<ref name="Porreca"/> Chemoreceptors in the CTZ relay information about the presence of emetic agents in the blood to the adjacent [[nucleus tractus solitarii]] (NTS).<ref name="Hornby">{{cite journal|last1=Hornby|first1=Pamela J.|title=Central neurocircuitry associated with emesis|journal=The American Journal of Medicine|date=December 2001|volume=111|issue=8|pages=106–112|doi=10.1016/S0002-9343(01)00849-X|pmid=11749934}}</ref> The relaying happens by the initiation of an action potential, which is caused by the chemoreceptor causing a change in electric potential in the neuron it is embedded in, which then subsequently causes an action potential. This happens constantly, so the chemoreceptors in the CTZ are continually sending information about how much emetic agents are in the blood, even when emesis is not signaled for. The NTS is organized into subnuclei that direct many different functions relating to swallowing, gastric sensation, laryngeal and pharyngeal sensation, [[baroreceptor]] function, and respiration.<ref name="Hornby"/> The NTS directs signals about these functions to a [[central pattern generator]] (CPG). This CPG actually coordinates the sequences of physical movements during emesis. The main neurotransmitters involved in communication between the CTZ and remaining vomiting center are serotonin, dopamine, histamine, and [[endogenous opioids]] which include [[endorphins]], [[enkephalins]], [[dynorphin]].

The CTZ communicates with the other parts of the vomiting center through neurons that contain [[5-HT3|5-HT<sub>3</sub>]], [[DRD2|D<sub>2</sub>]], [[HRH1|H<sub>1</sub>]] and [[HRH2|H<sub>2</sub>]] receptors.<ref name="Porreca"/>  It has been seen that intraventricular administration of histamine in dogs causes an emetic response.<ref name="Bhargava">{{cite journal|last1=Bhargava|first1=KP|last2=Dixit|first2=KS|title=Role of the chemoreceptor trigger zone in histamine-induced emesis|journal=British Journal of Pharmacology|date=November 1968|volume=34|issue=3|pages=508–13|doi=10.1111/j.1476-5381.1968.tb08479.x|pmid=4387255|pmc=1703476}}</ref> This shows that histamine plays a significant role in signaling for emetic action in the CTZ. Some classes of molecules have been shown to inhibit the emetic response due to histamine, these include [[mepyramine]], [[burimamide]] and [[metiamide]].<ref name="Bhargava"/>

===Phosphodiesterases===

Recent studies have found that [[phosphodiesterase]] 4 (PDE4) inhibitors, such as [[Rolipram]], cause emesis as one of their side effects.<ref name="Mori">{{cite journal|last1=Mori|first1=F|last2=Pérez-Torres|first2=S|last3=De Caro|first3=R|last4=Porzionato|first4=A|last5=Macchi|first5=V|last6=Beleta|first6=J|last7=Gavaldà|first7=A|last8=Palacios|first8=JM|last9=Mengod|first9=G|title=The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D|journal=Journal of Chemical Neuroanatomy|date=September 2010|volume=40|issue=1|pages=36–42|doi=10.1016/j.jchemneu.2010.03.004|pmid=20347962|hdl=10261/147758|s2cid=43192630|hdl-access=free}}</ref> It has been found that these PDE4 isoforms are expressed in the CTZ and in the brainstem in general.<ref name="Mori"/> The [[mRNA]] products from genes that code for these PDE4 isoforms are plentiful in the CTZ, and not only located in CTZ [[neurons]], but also in [[glial cells]] and blood vessels associated with the CTZ neurons.<ref name="Mori"/> PDE4 mRNAs are transcribed more in the area postrema and the CTZ than anywhere else in the brainstem.<ref name="Mori"/> The PDE4 degrades the phosphodiester bonds in the [[second messenger]] molecule [[cyclic adenosine monophosphate]] (cAMP), which is one of the ways the brain relays information. By modifying cAMP signaling in the CTZ, it is thought that this could mediate the emetic effects of PDE4 inhibitors in the CTZ.<ref name="Mori"/>

===H-channels===

Most of the neurons located in the CTZ express hyperpolarization-activated cation channels (H-channels).<ref name="Shinpo">{{cite journal|last1=Shinpo|first1=K|last2=Hirai|first2=Y|last3=Maezawa|first3=H|last4=Totsuka|first4=Y|last5=Funahashi|first5=M|title=The role of area postrema neurons expressing H-channels in the induction mechanism of nausea and vomiting|journal=Physiology & Behavior|date=20 August 2012|volume=107|issue=1|pages=98–103|doi=10.1016/j.physbeh.2012.06.002|pmid=22722099|s2cid=23070726}}</ref> Since the neurons in the CTZ convey information relating to emesis to the other parts of the vomiting center, it was thought that these H-channels might play a role in nausea and the emetic response. Recently, evidence of this notion that H-channels in CTZ neurons play a role in emesis has come to light. It has been found that ZD7288, which is a H-channel inhibitor, inhibited the acquisition of [[conditioned taste aversion]] (CTA) in rats and reduced [[apomorphine]]-induced [[c-Fos]] expression in the area postrema where the CTZ is located.<ref name="Shinpo"/> This suggests that the neurons that express H-channels in the CTZ and area postrema are involved in nausea and the emetic response.<ref name="Shinpo"/>