scholarly journals Prenatal nicotine exposure enhances the trigeminocardiac reflex via serotonin receptor facilitation in brainstem pathways

2013 ◽  
Vol 115 (4) ◽  
pp. 415-421 ◽  
Author(s):  
C. Gorini ◽  
H. Jameson ◽  
A. L. Woerman ◽  
D. C. Perry ◽  
D. Mendelowitz
Keyword(s):  
Receptor Antagonist ◽  
Trigeminal Nerve ◽  
Serotonin Receptor ◽  
Nucleus Ambiguus ◽  
Nicotine Exposure ◽  
Sprague Dawley ◽  
Trigeminocardiac Reflex ◽  
Brainstem Slice ◽  
Prenatal Nicotine Exposure ◽  
Prenatal Nicotine

In this study we used a rat model for prenatal nicotine exposure to test whether clinically relevant concentrations of brain nicotine and cotinine are passed from dams exposed to nicotine to her pups, whether this changes the trigeminocardiac reflex (TCR), and whether serotonergic function in the TCR brainstem circuitry is altered. Pregnant Sprague-Dawley dams were exposed to 6 mg·kg−1·day−1of nicotine via osmotic minipumps for the duration of pregnancy. Following birth dams and pups were killed, blood was collected, and brain nicotine and cotinine levels were measured. A separate group of prenatal nicotine-exposed pups was used for electrophysiological recordings. A horizontal brainstem slice was obtained by carefully preserving the trigeminal nerve with fluorescent identification of cardiac vagal neurons (CVNs) in the nucleus ambiguus. Stimulation of the trigeminal nerve evoked excitatory postsynaptic current in CVNs. Our data demonstrate that prenatal nicotine exposure significantly exaggerates both the TCR-evoked changes in heart rate in conscious unrestrained pups, and the excitatory neurotransmission to CVNs upon trigeminal afferent nerve stimulation within this brainstem reflex circuit. Application of the 5-HT1Areceptor antagonist WAY 100635 (100 μM) and 5-HT2A/Creceptor antagonist ketanserin (10 μM)significantly decreased neurotransmission, indicating an increased facilitation of 5-HT function in prenatal nicotine-exposed animals. Prenatal nicotine exposure enhances activation of 5-HT receptors and exaggerates the trigeminocardiac reflex.

Effect of prenatal nicotine exposure on biphasic hypoxic ventilatory response and protein kinase C expression in caudal brain stem of developing rats

2004 ◽  
Vol 96 (6) ◽  
pp. 2213-2219 ◽  
Author(s):  
Narong Simakajornboon ◽  
Vukmir Vlasic ◽  
Hong Li ◽  
Hemant Sawnani
Keyword(s):  
Brain Stem ◽  
Ventilatory Response ◽  
Whole Body ◽  
Current Evidence ◽  
Nicotine Exposure ◽  
Respiratory Drive ◽  
Hypoxic Ventilatory Response ◽  
Prenatal Nicotine Exposure ◽  
Pkc Β ◽  
Prenatal Nicotine

Current evidence suggests that maternal smoking is associated with decreased respiratory drive and blunted hypoxic ventilatory response (HVR) in the newborn. The effect of prenatal nicotine exposure on overall changes in HVR has been studied; however, there is limited data on the effect of nicotine exposure on each component of biphasic HVR. To examine this issue, 5-day timed-pregnant Sprague-Dawley rats underwent surgical implantation of an osmotic minipump containing either normal saline (Con) or a solution of nicotine tartrate (Nic) to continuously deliver free nicotine at 6 mg·kg of maternal weight-1·day-1. Rat pups at postnatal days 5, 10, 15, and 20 underwent hypoxic challenges with 10% O2 for 20 min using whole body plethysmography. At postnatal day 5, Nic was associated with attenuation of peak HVR; peak minute ventilaton increased 44.0 ± 6.8% (SE) from baseline in Nic pups, whereas that of Con pups increased 62.9 ± 5.1% ( P < 0.05). Nic pups also had a reduction in the magnitude of ventilatory roll-off; minute ventilation at 15 min decreased 7.3 ± 7.1% in Nic pups compared with 27.3 ± 4.0% in Con pups ( P < 0.05). No significant difference in HVR was noted at postnatal days 10, 15, and 20. Hypercapnic response was similar at all ages. We further investigated the effect of prenatal nicotine exposure on PKC expression in the caudal brain stem (CB) of developing rats. At postnatal day 5, Nic was associated with increased expression of PKC-β and PKC-δ in CB, whereas other PKC isoforms were not affected. It is concluded that prenatal nicotine exposure is associated with modulation of biphasic HVR and a selective increase in the expression of PKC-β and PKC-δ within the CB of developing rats.

scholarly journals Hydro ethanol extract of Holarrhena floribunda stem bark exhibits anti-anaphylactic and anti-oedematogenic effects in murine models of acute inflammation

2020 ◽  
Author(s):  
Stephen Antwi ◽  
Daniel Oduro-Mensah ◽  
David Darko Obiri ◽  
Newman Osafo ◽  
Aaron Opoku Antwi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
Acute Inflammation ◽  
Late Phase ◽  
Ethanol Extract ◽  
Stem Bark ◽  
Bark Extract ◽  
Prostaglandin E ◽  
Sprague Dawley ◽  
Anti Inflammatory

Abstract Background: Holarrhena floribunda stem bark has anecdotal use in Ghanaian folk medicine for management of inflammatory conditions. This study was conducted to investigate the in vivo anti-inflammatory activity of the bark extract using models of acute inflammation in male Sprague Dawley rats, C57BL/6 mice and 36 ICR mice. Methods: A 70 % hydro-ethanol extract of the stem bark (HFE) was evaluated at doses of 5–500 mg/kg bw. Local anaphylaxis was modelled by the pinnal cutaneous anaphylactic test. Systemic anaphylaxis or sepsis were modeled by compound 48/80 or lipopolysaccharide, respectively. Clonidine-induced catalepsy was used to investigate effect on histamine signaling. Anti-oedematogenic effect was assessed by induction with carrageenan. Effects on mediators of biphasic acute inflammation were studied using histamine and serotonin (early phase) or prostaglandin E2 (late phase).Results: HFE demonstrated anti-inflammatory and/or anti-oedematogenic activity comparable to standard doses of aspirin and diclofenac (inhibitors of cyclooxygenases-1 and -2), chlorpheniramine (histamine H1-receptor antagonist), dexamethasone (glucocorticoid receptor agonist), granisetron (serotonin receptor antagonist) and sodium cromoglycate (inhibitor of mast cell degranulation). All observed HFE bioactivities increased with dose.Conclusions: The data provide evidence that the extract of H. floribunda stem bark has anti-anaphylactic and anti-oedematogenic effects; by interfering with signalling or metabolism of histamine, serotonin and prostaglandin E2 which mediate progression of inflammation. The anti-inflammatory and antihistaminic activities of HFE may be relevant in the context of management of COVID-19.

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