Cellular sources, targets and actions of constitutive nitric oxide in the magnocellular neurosecretory system of the rat

Abstract

Nitric oxide (NO) is a key activity-dependent modulator of the magnocellular neurosecretory system (MNS) during conditions of high hormonal demand. In addition, recent studies support the presence of a functional consitutive NO tone. The aim of this study was to identify the cellular sources, targets, signalling mechanisms and functional relevance of constitutive NO production within the supraoptic nucleus (SON). Direct visualization of intracellular NO, along with neuronal nitric oxide synthase (nNOS) and cGMP immunohistochemisty, was used to study the cellular sources and targets of NO within the SON, respectively. Our results support the presence of a strong NO basal tone within the SON, and indicate that vasopressin (VP) neurones constitute the major neuronal source and target of basal NO. NO induced-fluorescence and cGMP immunoreactivity (cGMPir) were also found in the glia and microvasculature of the SON, suggesting that they contribute as sources/targets of NO within the SON. cGMPir was also found in association with glutamic acid decarboxylase 67 (GAD67)-and vesicular glutamate transporter 2 (VGLUT2)-positive terminals. Glutamate, acting on NMDA and possibly AMPA receptors, was found to be an important neurotransmitter driving basal NO production within the SON. Finally, electrophysiological recordings obtained from SON neurones in a slice preparation indicated that constitutive NO efficiently restrains ongoing firing activity of these neurones. Furthermore, phasically active (putative VP) and continuously firing neurones appeared to be influenced by NO originating from different sources. The potential roles for basal NO as an autocrine signalling molecule, and one that bridges neuronal-glial-vascular interactions within the MNS are discussed.

Tonic and stimulus-evoked nitric oxide production in the mouse olfactory bulb

“…It is becoming clear that basal NO production can play a variety of roles in regulating functions of neuronal circuits. For example, in supraoptic nucleus, NO tone generated by magnocellular neurons exerts inhibitory control over oxytocin and vasopressin systems (Stern and Zhang, 2005). During late pregnancy, nNOS mRNA is reduced and endogenous NO production markedly down-regulated, facilitating oxytocin release during parturition (Srisawat et al, 2000).…”

Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254

“…NO has been described as an activity-dependent modulator of the magnocellular neurosecretory system. We and others have shown that NO signaling is required for stimulated VP release from SON tissue punches (Gillard et al, 2007) and the latter serves to regulate MNC electrical activity and pituitary VP output (Kadowaki et al, 1994;Liu et al, 1998;Stern and Ludwig, 2001;Stern and Zhang, 2005). Moreover, nNOS expression and NOS activity (as assessed by NADPH-d) in MNCs appears to be responsive to physiological state, suggesting an activity-dependent role for NO signaling in the control of body water and salt balance.…”

“…Evidence also exists for NO involvement in the neurotoxic actions of organohalogens such as polybrominated diphenyl ethers (PBDEs). NO functions in both normal and pathological CNS processes associated with endocrine, homeostatic as well as synaptic functions (Dawson and Dawson, 1996;Garthwaite and Boulton, 1995;Stern and Zhang, 2005). There is evidence that most of the dual actions of NO may be targets of PCBs.…”

Heterogeneous distribution of basal cyclic guanosine monophosphate within distinct neuronal populations in the hypothalamic paraventricular nucleus

“…This is supported by recent studies indicating that inhibitors of nitric oxide synthase (NOS) activity within the PVN results in sympathoexcitation and increased blood pressure (76). Moreover, diminished basal NO availability within the PVN has been shown to contribute to elevated neurohumoral drive in pathological conditions such as hypertension, heart failure and diabetes (16,73,78).Accumulating evidence indicates that NO effects on neuroendocrine and autonomic outputs from the SON and PVN are mediated by inhibition of the electrical activity of both magnocellular (3,37,59,62) and preautonomic neurons (34, 35), respectively, and that these actions are mediated through an enhancement of GABAergic transmission (33,35,71). One of the classical mechanisms underlying NO signaling in neurons involves activation of soluble guanylyl cyclase (31).…”

“…Accumulating evidence indicates that NO effects on neuroendocrine and autonomic outputs from the SON and PVN are mediated by inhibition of the electrical activity of both magnocellular (3,37,59,62) and preautonomic neurons (34, 35), respectively, and that these actions are mediated through an enhancement of GABAergic transmission (33,35,71). One of the classical mechanisms underlying NO signaling in neurons involves activation of soluble guanylyl cyclase (31).…”