Histamine in Macaca mulatto monkey cardiac sympathetic nerve system: A morphological and functional assessment
Introduction
There is considerable evidence that histamine functions as a neurotransmitter in the central nervous system, and regulates numerous and important activities of the central nervous system (Schwartz et al., 1980, Fernandez-Novoa and Cacabelos, 2001, Zimatkin et al., 2003), while more and more evidence indicated that histamine was present in peripheral nervous system and that some neurons responded to it. The histamine-containing nerve fibers were found in the stomatogastric nervous system of the spiny lobster (Claiborne and Selverston, 1984), both rat and guinea pig gut (Panula et al., 1985), rat superior cervical ganglion and coeliac–superior mesenteric ganglion complex (Happola et al., 1985, Paivarinta et al., 1987), rat vas deferens pathway (Campos, 1988) and rat carotid body sensor cells (Koerner et al., 2004). Endogenous histamine also could excite neurons in the guinea pig superior cervical ganglion (Christian et al., 1989), and stimulate ischemically sensitive abdominal visceral afferents in cat (Fu et al., 1997). But at present little is known about the localization of histamine in the peripheral sympathetic nervous system of the nonhuman primates such as monkey.
Histamine produces a wide array of effects in the heart, including an increase in sinus rate (Levi et al., 1981) and the force of ventricular contraction (Hattori, 1999) through histamine H2 receptor, decrease in atrioventricular conduction velocity through histamine H1 receptor (Levi et al., 1975), and provokes arrhythmogenic effects on the sinus node, atrial fibers, AV node, Purkinje fibers, and ventricular cells (Wolff and Levi, 1986). While in experimental models of acute myocardial ischemia, concentrations of histamine in the coronary sinus increase concomitant with the development of early ischemia-induced ventricular arrhythmias (Wolff and Levi, 1988). The cause of dysfunction in myocardial ischemia was recognized as sympathetic overactivity accompanied by excessive norepinephrine (NE) release within the heart. Adrenergic nerves possess inhibitory receptors, such as α2-adrenoceptors, and histamine H3 receptors. Our and other's results demonstrated that activation of histamine H3 receptor could reduce NE release from cardiac sympathetic nerves (Luo et al., 1991, Imamura et al., 1996). Our previous study demonstrated the co-localization of histamine with NE within superior cervical ganglia (SCG), and the release of histamine from sympathetic nerve endings of guinea pig evoked by stimulations (Li et al., 2004, Li et al., 2006). In the light of this preceding work, the aim of the present study was to directly demonstrate whether the histamine can be biosynthesized, stored and released from the monkey cardiac sympathetic nerve endings as a possible newly discovered neurotransmitter, and to investigate the modulation of the endogenous histamine release through histamine H3 receptor in the cardiac nerve system.
Section snippets
Animals preparation
The experiments were carried out on male Macaca mulatto monkeys (Qiling, Henan, China) aged 4–8 years, ranging in weight from 5 to 13 kg. The monkeys were fed a standard primate diet with free access to reverse osmosis water. All experiments were approved by the Animal Care and Use Committee of the Fourth Military Medical University.
The animals were anaesthetized with pentobarbital (30 mg/kg, ip). The SCG were removed and fixed by 4% paraformadehyde, 10 μm-thick sections were cut using a
Co-localization of histamine and NE in the superior cervical ganglia
In sections of Macaca mulatto monkey SCG, the typical appearance of principal nerve cells was shown with haematoxylin and eosin staining. The co-localization of histamine and NE was examined by a double immunofluorescence. Immunoreactivities of histamine or NE were observed in the neuronal soma of principal nerve cells within SCG of Macaca mulatto monkey (Fig. 1). The co-existence of histamine and NE was identified in the same neuronal cell.
Characterization of histamine released from cardiac synaptosomes
Depolarization of cardiac synaptosomes with high
Discussion
Two-compartment peripheral storage for histamine has been suggested previously: a slow turnover mast cell compartment and a fast turnover non-mast cell compartment (Mcdonald and Blewett, 1981). In the rat right atrium, α-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, significantly decreased the histamine content but had no significant effect on the histamine content of the right atrium in rats pretreated with 6-hydroxydopamine, and the selective β1-adrenoceptor
Acknowledgements
This work has been partially supported by The Natural Science Foundation of PR China (98/39900075) and (03/30300104). We would like to thank Prof. Jingshan Zhang and Mrs. Chen Dan for excellent technical assistance.
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Li M and Hu J contribute to this work equally.