Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.
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PMID:Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes. 1145 9

Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related excitatory inputs under normal conditions. However, excitatory purinergic and serotonergic pathways are recruited during inspiratory activity after episodes of hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to dramatically change cardiorespiratory responses and decrease the ability to resuscitate from H/H. This study tested whether PNN exposure alters excitatory neurotransmission to CVNs in the nucleus ambiguus during and after H/H. Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded in CVNs from rats that were exposed to nicotine (6 mg x kg(-1) x d(-1)) throughout the prenatal period. In contrast to unexposed animals, in PNN animals H/H recruited excitatory neurotransmission to CVNs during inspiratory-related activity that was blocked by the alpha3beta4 nicotinic acetylcholine receptor (nAChR) blocker alpha-conotoxin AuIB (alpha-CTX AuIB, 100 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 microM) and d(-)-2-amino-5-phosphonopentanoic acid (AP5, 50 microM), selective AMPA/kainate and N-methyl-d-aspartate receptor blockers, respectively. Following H/H, there was a significant increase in inspiratory-related excitatory postsynaptic currents that were unaltered by alpha-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (100 microM), a purinergic receptor blocker and CNQX and AP5. The results from this study demonstrate that with PNN exposure, an excitatory neurotransmission to CVNs is recruited during H/H that is glutamatergic and dependent on activation of alpha3beta4-containing nAChRs. Furthermore, exposure to PNN abolishes a serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced by recruitment of a glutamatergic pathway to CVNs post H/H.
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PMID:Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and after hypoxia and hypercapnia with prenatal nicotine exposure. 1909 27