PubMed Health⌕ Search

Biomedical subjects

J E Maggio

Publications and source records attributed to J E Maggio.

71 records · Page 4Linked to original sources

The regional distribution of kassinin-like immunoreactivity in central and peripheral tissues of the cat.

The regional distribution of kassinin-like immunoreactivity (KLI) was investigated by radioimmunoassay in central and peripheral tissues of the cat. In the cat brain KLI was found to have a widespread distribution with the highest concentrations present in the substantia nigra followed by the hypothalamus and caudate nucleus. Moderate levels were detected in the spinal cord, brainstem and thalamus but only low levels were found in the frontal cortex and cerebellum. In the periphery KLI was present in moderate amounts in the pituitary but in only low amounts in the dorsal root ganglion. KLI was present throughout the gastrointestinal tract with the highest concentration in the duodenum. The distribution of KLI was found to resemble closely that of substance P-like immunoreactivity (SPLI) although the ratio of SPLI to KLI varied widely throughout the tissues tested. In the frontal cortex and cerebellum the concentration of SPLI was at least 5-fold higher than that of KLI whereas in the pituitary gland, caudate nucleus and terminal ileum the concentrations of SPLI were only 50% higher. High pressure liquid chromatographic analysis of individual tissue extracts was used in order to characterize the KLI. In the caudate nucleus, substantia nigra and hypothalamus the major immunoreactive peak co-eluted with synthetic substance K. In contrast, in the spinal cord and terminal ileum the major peak of KLI co-eluted with synthetic neuromedin K. These results demonstrate that KLI is widely distributed throughout cat tissues and that this distribution closely resembles that of SPLI. However, it also appears that there are important qualitative differences in the KLI between the areas tested.

Adrenal Glands↗

Substance K and substance P in the ventral tegmental area.

A comparison was made between substance P (SP) and substance K (SK) in the ventral tegmental area (VTA) (A10 dopamine cell group) of the rat. Approximately equal densities of SP and SK-immunoreactive neuronal fibers were observed. However, while previous reports demonstrate negligible density of autoradiographically defined SP receptors in the VTA, we observed a high density of SK receptors. SK or SP was microinjected into the VTA, and changes in spontaneous motor activity were measured using a photocell apparatus. SK was found to be at least 10 times more potent than SP in producing an increase in motor activity. These data suggest that while both SK and SP are present in the VTA, SK may have a more significant physiological role in modulating dopamine neurons in the ventromedial mesencephalon.

Animals↗

Substance K and substance P differentially modulate mesolimbic and mesocortical systems.

The newly discovered peptide substance K (SK) is an aliphatic tachykinin structurally related to the aromatic tachykinin substance P (SP). Immunohistochemical examination showed a close association between SK afferents and dopamine (DA) cell bodies. Examination of the possible role of SK in modulating midbrain DA systems revealed that SP, but not SK, is associated with the stress response of the mesocortical system. Ventral tegmental area injections of SK effected locomotor hyperactivity, a mesolimbic-mediated behavior. Ventral tegmental injections of SP, but not SK, activated DA metabolism in the prefrontal cortex, while SK injections altered DA metabolism in the nucleus accumbens, but not the cortical site. These data suggest that SK and SP may differentially modulate the mesolimbic and mesocortical systems.

Animals↗

"Kassinin" in mammals: the newest tachykinins.

Until recently, substance P was widely believed to be the only mammalian representative of the tachykinin peptide family. In 1983, however, four independent groups using three different approaches reported that mammalian tissues also contain two novel tachykinins which resemble the amphibian tachykinin kassinin in both C-terminal sequence and pharmacology. Thus, the discovery of an active peptide in anuran skin has once again preceded the discovery of its mammalian analogs. While the discovery of the new peptides, substance K and neuromedin K, has clarified some issues in substance P research, it has raised some questions about others. With hindsight, it is clear that some of the activities once thought to be mediated by substance P may in fact be mediated by another mammalian tachykinin. Current knowledge of tachykinins and their receptors in mammals represents only a lower limit on the complexity of the system. This review summarizes recent progress in a rapidly developing field.

Amino Acid Sequence↗

A pharmacological study with substance K: evidence for multiple types of tachykinin receptors.

The substance P antagonist [D-Arg,D-Pro,D-Trp,Leu]SP (RPTTL-SP) produced a simple competitive antagonism of the responses to substance K (SK) and substance P (SP) in a variety of tissues. In the guinea-pig ileum and field stimulated rat vas deferens the pKB values against SK were similar to those against SP indicating a single population of receptors. In the guinea-pig urinary bladder the pKB value against SK was significantly higher suggesting the existence of at least two subtypes of tachykinin receptor in this tissue. In the hamster urinary bladder no antagonism was observed with up to 30 microM RPTTL-SP indicating the possibility of a third type of receptor.

Animals↗

Substance P receptors: localization by light microscopic autoradiography in rat brain using [3H]SP as the radioligand.

Substance P (SP) is a putative neurotransmitter in both the peripheral and central nervous systems. In the present report we have used a modification of the Young and Kuhar technique to investigate some of the SP receptors binding properties and the distribution of SP receptors in rat brain. Tritiated SP [( 3H]SP) absorbed extensively to glass but this adsorbtion was greatly reduced by preincubating the slide-mounted tissue sections in a solution containing the cationic polymer polyethylenimine. [3H]SP was found to bind to rat tissue in a saturable fashion with a Bmax of 14.7 fmol/mg tissue wet weight and a Kd of 1.1 nM. The rank order of potencies for displacing [3H]SP binding from rat tissue sections was SP greater than SP sulphoxide greater than DiMeC7 greater than Eledoisin greater than SP(5-11) greater than SP(COOH) greater than SP(1-9) amide. Using autoradiography coupled with LKB tritium-sensitive Ultrofilm or the dry emulsion-coated coverslip technique the distribution of [3H]SP binding sites was found to be very dense within olfactory bulb, amygdalo-hippocampal area and the nucleus of the solitary tract. Heavy concentrations of receptors were observed in the septum, diagonal band of Broca, striatum subiculum, hypothalamus, locus coeruleus, parabrachial nucleus and lobule 9 and 10 of the cerebellum. Moderate to low concentrations of receptors were observed in the cerebral cortex, globus pallidus, raphe nuclei and the trigeminal nucleus. Very low densities were observed in most aspects of the dorsal thalamus, substantia nigra and cerebellum (other than lobule 9 and 10). Comparisons of the present data with SP peptide levels indicate that in some areas of the brain there is a rough correlation between peptide and receptor levels. However, in other brain areas (olfactory bulb, globus pallidus and substantia nigra) there is little obvious correlation between the two.

Animals↗

Regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues and the effect of capsaicin.

The regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues was investigated by radioimmunoassay and found to resemble closely that of substance P-like immunoreactivity. Neonatal capsaicin treatment caused a similar decrease to both kassinin-like and substance P-like immunoreactivity in primary sensory areas. These results suggest that more than one member of the tachykinin family of neuropeptides exist within the same neuron.

Animals↗

The autoradiographic distribution of kassinin and substance K binding sites is different from the distribution of substance P binding sites in rat brain.

In the present report we have used autoradiographic receptor binding techniques to compare the distribution of substance K (SK), kassinin (K) and substance P (SP) binding sites in the rat brain. Whereas the distribution of K and SK binding sites appeared to be identical, notable differences are apparent when comparing these binding sites to the distribution of SP binding sites. These results demonstrate that in many areas of the rat brain K and SK binding sites have a different distribution than SP binding sites. These results further suggest that different classes of mammalian tachykinins may each have their own set of receptors.

Animals↗

Evidence for vasoactive intestinal polypeptide as a neurotransmitter in smooth muscle of the urogenital tract.

The localization of vasoactive intestinal polypeptide (VIP) in the anococcygeus muscle of the rat, rabbit and cat was investigated by radioimmunoassay and immunohistochemistry. High concentrations of VIP-like immunoreactivity were found in the anococcygeus muscle of all 3 species. VIP-like immunoreactivity was observed in a network of nerve fibres branching throughout the muscle which were unaffected by treatment with 6-hydroxydopamine. VIP, when applied exogenously to isolated preparations of the anococcygeus, produced dose-related relaxations of tone in all 3 species with a time course and maximum response similar to non-adrenergic, non-cholinergic inhibitory nerve stimulation. These observations provide further evidence in support of VIP as a suitable candidate for the non-adrenergic, non-cholinergic inhibitory neurotransmitter in the anococcygeus muscle.

Anal Canal↗

Structure of a mycobacterial polysaccharide-fatty acyl-CoA complex: nuclear magnetic resonance studies.

MMP, a linear alpha 1 leads to 4 linked polymer of 3-O-methylmannose, regulates the fatty acid synthetase from Mycobacterium smegmatis by forming stoichiometric complexes with the long-chain acyl-CoA synthetase products. In agreement with previous proposals [Bloch, K. (1977) in Advances in Enzymology and Related Areas of Molecular Biology, ed. Meister, A. (Wiley, New York), Vol. 45, pp. 1-84], nuclear magnetic resonance studies show that the polysaccharide, a random coil in its free form, undergoes a major conformational transition upon enclosing long-chain acyl-CoA. The polysaccharide, probably in helical conformation in the complexed form, interacts with both the paraffinic chain and the CoA moieties of the included fatty acyl thioester.

Acyl Coenzyme A↗

A novel radioimmunoassay for neuromedin K. I. Absence of neuromedin K-like immunoreactivity in guinea pig ileum and urinary bladder. II. Heterogeneity of tachykinins in guinea pig tissues.

A novel and highly specific radioimmunoassay for the tachykinin peptide neuromedin K (NMK, also known as neurokinin beta, neurokinin B) has been developed and used to determine the distribution of this peptide in extracts of guinea pig tissues. In addition to immunoreactive components coeluting with the 3 mammalian tachykinins, substance P (SP), substance K (SK) and NMK, analyses using reverse-phase HPLC revealed immunoreactive peaks coeluting with the C-terminal octapeptide of SK (SK-(3-10], an N-terminally extended form of SK (gamma-preprotachykinin-(72-92)amide), and a yet unidentified peak eluting before NMK in the extracts of guinea pig brain and spinal cord. In contrast to the other tachykinins, SP and SK, which were present in high concentrations in extracts of all peripheral and central tissues examined, NMK-like immunoreactivity was detected only in extracts of central tissues. NMK-like immunoreactivity was not detected in extracts of terminal ileum and urinary bladder.

Animals↗

Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: 1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; 2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; 3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and 4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells.

Amino Acid Sequence↗

The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes.

Previous work has established that the central nervous system can modulate the immune response. Direct routes through which this regulation may occur are the sympathetic and sensory innervation of lymphoid organs. We investigated the innervation of canine mesenteric lymph nodes using immunohistochemistry and the expression of binding sites for sensory neuropeptides using quantitative receptor autoradiography. The sympathetic innervation of lymph nodes was examined by immunohistochemical methods using an antiserum directed against tyrosine hydroxylase (TOH), the rate limiting enzyme in catecholamine synthesis. TOH-containing fibers were associated with 90% of the blood vessels (arteries, veins, arterioles and venules) in the hilus, medullary and internodular regions of lymph nodes and in trabeculae with no obvious relationship to blood vessels. The sensory innervation of lymph nodes was investigated using antisera directed against the putative sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP- and SP-containing fibers were detected in the hilus, the medullary region, and the internodular region of lymph nodes usually in association with arterioles and venules. About 50% of the arterioles and venules exhibited a CGRP innervation and a smaller fraction (5-10%) were innervated by SP-containing fibers. Few if any TOH, CGRP, and SP nerve fibers were detected in the germinal centers of lymph nodes. Using quantitative receptor autoradiography we studied the distribution of receptor binding sites for the sensory neuropeptides CGRP, SP, substance K (SK), vasoactive intestinal peptide (VIP), somatostatin (SOM), and bombesin. Specific CGRP binding sites were expressed throughout lymph nodes by trabeculae, arterioles, venules and 25% of the germinal centers. SP receptor binding sites were localized to arterioles and venules in the T cell regions and 25-30% of the germinal centers. VIP binding sites were localized to the internodular and T cell regions, to medullary cords, and to 10-20% of germinal centers. SK, SOM, and bombesin binding sites were not detected in the lymph nodes, although receptor binding sites for these peptides were detected with high specific/nonspecific binding ratios in other canine peripheral tissues. Taken together with previous results these findings suggest that the sympathetic and sensory innervation of mesenteric lymph nodes appears to be involved with the regulation of their blood and lymph flow. The neuropeptide receptor binding sites in lymph node germinal centers may be expressed by lymphocytes upon activation by antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Heterogeneity of tachykinin-like immunoreactive peptides in rat spinal cord and dorsal root ganglia.

The concentrations of tachykinins in rat spinal cord and dorsal root ganglia (DRGs) were measured using a combination of high performance liquid chromatography (HPLC) and radioimmunoassays (RIAs). Substance P-like immunoreactivity (SPLI) was found to be significantly higher than either substance K-like immunoreactivity (SKLI) or neuromedin K-like immunoreactivity (NMKLI) in both tissues. In the spinal cord, the concentration of SKLI was comparable to that of NMKLI. In DRGs, NMKLI is present at concentrations much lower than those of SKLI or SPLI. In addition to immunoreactive components co-eluting with the three mammalian tachykinins SP, SK and NMK, analyses using reverse-phase HPLC revealed an immunoreactive peak co-eluting with the C-terminal octapeptide of SK (SK3-10), and a yet to be identified peak eluting before SK. This study also demonstrates the use of a novel and highly specific RIA for NMK to measure NMKLI without the need of reverse-phase HPLC.

Animals↗

Receptors for sensory neuropeptides in human inflammatory diseases: implications for the effector role of sensory neurons.

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.

Animals↗

Immunocytochemical localization of neuromedin K (neurokinin B) in rat spinal ganglia and cord.

Specific antisera directed against substance P and neuromedin K (neurokinin B) have been used in double-label immunofluorescence studies to unambiguously localize these two neuropeptides of the tachykinin family in single tissue sections of rat spinal cord and dorsal root ganglia. Substance P-like immunoreactivity (SPLI) is present but neuromedin K-like immunoreactivity (NMKLI) is undetectable in dorsal root ganglia. Both peptides are present in the spinal cord, but NMKLI is largely restricted to the dorsal gray while SPLI shows a broader distribution. In the spinal gray, NMKLI coexists with SPLI in some, but not all, fibers. While substance P in the dorsal spinal cord is largely of primary afferent origin, neuromedin K appears to originate largely from intrinsic spinal neurons.

Animals↗