Search PubMed⌕ Search

Biomedical subjects

S Vanhatalo

Publications and source records attributed to S Vanhatalo.

46 records · Page 3Linked to original sources

Axonal transport of nitric oxide synthase in autonomic nerves.

By using mechanical nerve ligation or nerve pinch technique, we provide evidence that nitric oxide synthase (NOS) is transported in the preganglionic sympathetic axons, while postganglionic axons lack NOS transport. This finding corroborates the preganglionic sympathetic terminal as the site of NO synthesis, which is known to affect ganglionic transmission. Both vasoactive intestinal polypeptide (VIP) and substance P (SP) containing neurons of the nodose ganglion transport NOS in their axons. These results therefore suggest that NOergic innervation of autonomically innervated tissues is of parasympathetic and/or sensory, rather than sympathetic, origin.

Animals↗

Nitric oxide-synthesizing neurons originating at several different levels innervate rat penis.

While the crucial role of neurally produced nitric oxide in mediating penile erection is well established, the understanding of the peripheral neuroanatomy of the nitric oxide-ergic pathways is still incomplete. This study was designed to elucidate further the distribution of nitric oxide synthase, and its relation to the distribution of neuropeptides and tyrosine hydroxylase in all penis-projecting neural pathways. A triple-labelling technique was employed, with the retrograde tracer Fluoro Gold combined with neuropeptide immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, a marker of nitric oxide synthase. The presence within the penis of scattered nerve cell bodies exhibiting NADPH-diaphorase activity was revealed. Most (76%) of the penis-projecting neurons in the major pelvic ganglion exhibited NADPH-diaphorase activity and immunoreactivity to vasoactive intestinal peptide, while none of them contained tyrosine hydroxylase. Sympathetic paravertebral postganglionic neurons, in turn, contained tyrosine hydroxylase, but did not exhibit NADPH-diaphorase activity. In the afferent, sensory neurons projecting to the penis from the dorsal root ganglia, NADPH-diaphorase activity coexisted with immunoreactivity to both substance P (8%) and calcitonin gene-related peptide (26%). Preganglionic neurons originating in the spinal cord intermediolateral column at the thoracolumbar level T11-L3 terminated, not only in the major pelvic ganglion, but also within the penis. The majority (81%) of the penis-projecting neurons exhibited NADPH-diaphorase activity. The results indicate that the rat penis receives several different nitric oxide-ergic neural projections. It is therefore possible that nitric oxide affects penile erection at several neuronal levels.

Animals↗

Direct nitric oxide-containing innervation from the rat spinal cord to the penis.

Nitric oxide synthase (NOS)-immunoreactive pathways to the rat penis were studied by combining retrograde tracing by Fluorogold with NOS immunohistochemistry. Injection of the tracer into the penile shaft resulted in Fluorogold labelling in a vast number of NOS-immunoreactive neurons in the major pelvic ganglion. In addition, some neurons in the spinal cord intermediolateral column consistently contained Fluorogold label in the upper lumbar levels. Most of these neurons were also NOS-immunoreactive. These findings suggest that the sympathetic preganglionic, NOS-containing neurons project to the penis, and they may participate in nitric oxide-mediated penile erection.

Adrenergic Fibers↗

Co-localization of NADPH diaphorase reactivity and vasoactive intestinal polypeptide in human colon.

Nitric oxide-containing nervous structures were localized in the human colon using NADPH diaphorase activity and nitric oxide synthase immunoreactivity. We found some, solitary NADPH diaphorase-reactive and nitric oxide synthase-immunoreactive neurons in the submucous plexus, while the myenteric plexus contained several neurons, often arranged in clusters, and nerve fibers showing these markers. The circular muscle layer contained a dense plexus of NADPH diaphorase-reactive nerves, which was greater than that in the longitudinal muscle layer. We report on co-localization of NADPH diaphorase activity and VIP immunoreactivity in several neurons of the myenteric ganglia. Such co-localization has not been reported previously for human colon. Localization of nitric oxide synthase and VIP in the myenteric plexus and in the nerves of circular muscle layer raises the possibility that nitric oxide contributes to the regulation of motility in the human colon.

Colectomy↗

Dopaminergic periventriculo-hypophyseal nerves show tryptophan-hydroxylase immunoreactivity but lack serotonin synthesis.

Hypothalamic dopaminergic periventricular and arcuate nuclei are known to project to the pituitary gland and contain serotonin in their terminals. In order to elucidate the potential of these neurons to synthesize serotonin, we studied immunohistochemically the possible tryptophan hydroxylase content of periventriculo-hypophyseal neurons, identified by retrograde tracing from the pituitary gland. These neurons were found to contain tryptophan hydroxylase-immunoreactivity (TpOH-IR), which was enhanced after colchicine treatment. All of the TpOH-IR neurons contained tyrosine hydroxylase-immunoreactivity as well. However, none of them were immunoreactive for serotonin in either intact animals or in animals pretreated with serotonin precursor L-tryptophan and MAO inhibitor pargyline. Thus, neurons of the dopaminergic periventriculo-hypophyseal pathway express tryptophan hydroxylase, but are unable to synthesize serotonin. These findings (i) raise the possibility that, in these nerves, serotonin might serve a function other than regular synaptic transmission, and (ii) suggest that expression of an enzyme synthesizing certain transmitter does not necessarily confirm the corresponding transmitter phenotype of that neuron.

Animals↗

Colocalization of dopamine and serotonin in the rat pituitary gland and in the nuclei innervating it.

The nerve terminals in the intermediate and posterior lobes of the rat pituitary gland are reported to show colocalization of serotonin and tyrosine hydroxylase. This study examined the extent of this colocalization in the pituitary gland and in the nuclei considered to project to the pituitary. In the intermediate lobe, two types of nerve fibers were encountered, one containing serotonin (5-HT-IR) and tyrosine hydroxylase (TH-IR) immunoreactivities and the other showing 5-HT-IR only. Instead, there was no colocalization in the posterior lobe. In the hypothalamus, colchicine treatment with L-tryptophan and pargyline injections resulted in 5-HT-IR in some neurons in the dorsomedial, periventricular and arcuate nuclei, some of which in the arcuate and periventricular nuclei were also TH-IR. In the raphe nuclei no colocalization of 5-HT-IR and TH-IR was observed. Catecholamine neurotoxin, 6-hydroxydopamine, abolished the 5-HT-IR and dramatically reduced the TH-IR in the intermediate lobe nerve fibers. Both effects were prevented by cocaine, a monoamine uptake inhibitor, but not by fluoxetine, a specific serotonin uptake inhibitor. Serotonin neurotoxin p-chloroamphetamine (PCA) had no effect on intermediate lobe fibers, although it caused complete disappearance of 5-HT-IR from the posterior lobe nerve fibers. This effect was prevented by fluoxetine. Our results indicate, that colocalization of serotonin and TH observed in the intermediate lobe occurs both in the nerve terminals within the lobe and in some nuclei that innervate it. Furthermore, drug treatments suggest that serotonin in the intermediate lobe is localized in catecholaminergic fibers, which do not posses a specific serotonin uptake mechanism.

Animals↗

Release of false transmitter serotonin from the dopaminergic nerve terminals of the rat pituitary intermediate lobe.

Rat pituitary intermediate lobe contains two types of serotonin-immunoreactive nerve terminals. Most of them are dopaminergic, in which serotonin acts as a false transmitter, while the rest are true serotoninergic nerves. In the present study, release of the false transmitter serotonin from the dopaminergic nerve terminals was studied by loading the neurons in vivo with serotonin precursor L-tryptophan and MAO inhibitor pargyline, which results in accumulation of false transmitter serotonin. Subsequently pituitary neurointermediate lobe complexes were incubated in the presence of various agents. Potassium induced dramatic release of serotonin. This release was Ca(2+)-dependent, as demonstrated by an inhibition by Mg2+, and transporter-independent, since it was unaffected by GBR 12909 (a dopamine transport inhibitor). Tyramine and sodium nitroprusside, a nitric oxide donor, caused slight to remarkable release of serotonin. This release was inhibited by GBR 12909, suggesting that it was transporter-dependent. Presynaptic stimulation with apomorphine or haloperidol, dopamine receptor agonist or antagonist, respectively, or isoproterenol, agonist of the beta-adrenergic receptor, did not significantly release serotonin. Thus, it seems that presynaptic receptors per se cannot induce release of significant amounts of serotonin from the IL dopaminergic fibers. Our results suggest that false transmitter serotonin in the IL dopaminergic nerve terminals is released primarily by the classical exocytotic release mechanism, but may also be partly released by the transporter-dependent, non-exocytotic release.

Animals↗

Nitric oxide synthase in the hypothalamo-pituitary pathways.

Several histochemical and physiological studies in the literature suggest that nitric oxide (NO) is involved in the posterior pituitary regulation. This study was set out to demonstrate the distribution of the pituitary projecting nitric oxide containing hypothalamic pathways. The fluorescent retrograde tracer fluorogold (FG) was injected into the pituitary gland in order to reveal the hypothalamic nuclei projecting to the pituitary gland. Nitric oxide synthase (NOS) was subsequently visualized from the same sections by NADPH-diaphorase histochemistry. More than 70% of the FG labelled neurons in the preoptic area, paraventricular, supraoptic, retrochiasmatic, anterior commissural and circular nuclei as well as in many other small neurosecretory centers in the hypothalamus contained also NADPH-diaphorase activity (NADPH-DA). In addition, some of the neurons in the periventricular nucleus as well as occasional neurons in the lateral hypothalamus projecting to the pituitary gland contained NADPH-DA. The present results give the first systematic neuroanatomical description of the hypothalamic NO synthase containing neurons projecting into the pituitary gland. They indicate that the pituitary receives a widely distributed NO innervation, which originates mostly in the magnocellular neurosecretory hypothalamo-pituitary system. In addition, the finding that some presumably non-neurosecretory pituitary-projecting neurons contain NO as well suggests that NO might be a more widely used regulator of the posterior pituitary secretion than previously expected.

Amino Acid Oxidoreductases↗

NADPH-diaphorase activity and its colocalization with transmitters and neuropeptides in the postganglionic neurons of the rat superior cervical ganglion.

NADPH-diaphorase activity (NADPH-DA), a marker of neural nitric oxide synthase, was found in many postganglionic nerve cell bodies in the adult rat superior cervical ganglion (SCG) after colchicine treatment, postganglionic nerve trunk ligation or ganglion culture. NADPH-DA colocalized with immunoreactivity to tyrosine hydroxylase (TH), serotonin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), methionine-enkephalin and somatostatin. Almost all cells showing NADPH-DA were TH-immunoreactive, although several TH-immunoreactive cells lacked NADPH-DA. While suggesting that nitric oxide has an important role in the neuronal modulation in the synaptic transmission in the rat SCG, our results point out that nitric oxide synthesis is confined to a subpopulation of ganglion neurons. Our findings confirm the idea that the superior cervical ganglion consists of several subpopulations in which noradrenaline is colocalized with other transmitter or neuropeptide. Only about one-fourth of serotonin-immunoreactive neurons contained NADPH-DA. Similarly, the neuropeptides studied showed only partial colocalization with NADPH-DA. Our results thus suggest that nitric oxide is not associated with any particular transmitter or peptide.

Animals↗

Pharmacological characterization of serotonin synthesis and uptake suggest a false transmitter role for serotonin in the pituitary intermediate lobe.

A subpopulation of nerve fibers in the rat pituitary intermediate lobe (IL) have been shown to exhibit colocalization of serotonin (5-HT-IR) and tyrosine hydroxylase immunoreactivities and they are sensitive to neurotoxins specific to catecholamine neurons. This study was set out to examine the uptake and synthesis mechanisms of serotonin in these fibers. We developed an in vitro technique in which the neurointermediate lobe explants were incubated (14 and 48 h) in the presence of various drugs and serotonin was subsequently visualized by immunohistochemistry. Control incubation in the presence of serotonin (10(-6) M) resulted in a rich plexus of 5-HT-IR fibers in both posterior and intermediate lobes. Fluoxetine and citalopram (10(-6) M and 10(-5) M), inhibitors of 5-HT transporter, did not affect 5-HT-IR in the IL fibers, unless they were used in concentrations high enough (10(-4) M and 10(-3) M) to block unspecifically a number of monoamine transporters. The same applied for desipramine (10(-5)-10(-7) M), an inhibitor of the noradrenaline transporter. However, cocaine (10(-5)-10(-6) M) blocked serotonin uptake into these terminals, suggesting that serotonin uptake occurs through a dopamine transporter. Incubation of the IL in presence of L-tryptophan (10(-4) M) did not result in 5-HT-IR in the IL fibers showing colocalization of 5-HT-IR and tyrosine hydroxylase, which suggests that these fibers do not synthesize serotonin. The present results suggest that serotonin is taken up into the IL terminals by a dopamine transporter and is not synthesized in them, at least in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗