Faculty Collaboration Database

5-HT induces enhanced phrenic nerve activity via 5-HT(2A) receptor/PKC mechanism in anesthetized rats. Eur J Pharmacol 2011 Apr 25;657(1-3):67-75

Date

02/08/2011

Pubmed ID

21296069

DOI

10.1016/j.ejphar.2011.01.048

Scopus ID

2-s2.0-79952484387 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Respiratory behavior expresses diverse forms of plasticity by altering breathing patterns. Failure of respiratory neuroplasticity often leads to malfunctions. Long-term facilitation (LTF), the most frequently studied model induced by episodic hypoxia to produce long-lasting enhancement of phrenic motor output, is thought to be serotonin 2A (5-HT(2A)) receptor-dependent. Previous studies have described 5-HT-induced prompt apnea in intact animals. However, the role of exogenous 5-HT in mediating respiratory neuroplasticity is less attended in vivo study. We hypothesized that an in vivo 5-HT challenge contributes to respiratory neuroplasticity. Here, we found that systemic bolus administration of 5-HT exerted an initial transient inhibition followed by marked facilitation, forming a biphasic pattern of phrenic nerve activity in artificially ventilated, midcervically vagotomized, and anesthetized adult rats. The facilitatory phase corresponded to the enhanced phrenic nerve activity that lasted for at least one hour after drug exposure, characterized as phrenic LTF (pLTF). The 5-HT-induced biphasic pattern and pLTF were 5-HT(2A) receptor-dependent and coupled to protein kinase C (PKC) activation. The initial inhibition of phrenic nerve activity was found to be nodose ganglion-associated, whereas the subsequent facilitation was carotid body-associated, establishing a peripheral inhibitory-facilitatory afferent balance. Immunoreactive expressions of 5-HT/5-HT(2A) receptors and phospho-PKC isoforms/PKC substrate provide morphological evidence of existence of a 5-HT/5-HT(2A) receptor/PKC mechanism in the nodose ganglion and the carotid body. We speculate that 5-HT challenge in vivo may contribute to respiratory neuroplasticity, to yield pLTF or augmented pLTF in animals with reduced or absent peripheral inhibitory inputs.

Author List

Liu J, Wei X, Zhao C, Hu S, Duan J, Ju G, Wong-Riley MT, Liu Y

MESH terms used to index this publication - Major topics in bold

Anesthesia
Animals
Carotid Body
Female
Gene Expression Regulation
Isoenzymes
Ketanserin
Male
Neuronal Plasticity
Nodose Ganglion
Phosphoproteins
Phrenic Nerve
Protein Kinase C
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2A
Respiratory System
Serotonin
Serotonin Antagonists
Staurosporine