Mapping of neurokinin b in the cat brainstem.

We studied the distribution of neurokinin B-immunoreactive cell bodies and fibers in the cat brainstem using an indirect immunoperoxidase technique. The highest density of immunoreactive fibers was found in the motor trigeminal nucleus, the laminar and alaminar spinal trigeminal nuclei, the facial nucleus, the marginal nucleus of the brachium conjunctivum, the locus coeruleus, the cuneiform nucleus, the dorsal motor nucleus of the vagus, the postpyramidal nucleus of the raphe, the lateral tegmental field, the Kölliker-Fuse nucleus, the inferior central nucleus, the periaqueductal gray, the nucleus of the solitary tract, and in the inferior vestibular nucleus. Immunoreactive cell bodies containing neurokinin B were observed, for example, in the locus coeruleus, the dorsal motor nucleus of the vagus, the median division of the dorsal nucleus of the raphe, the lateral tegmental field, the pericentral nucleus of the inferior colliculus, the internal division of the lateral reticular nucleus, the inferior central nucleus, the periaqueductal gray, the postpyramidal nucleus of the raphe, and in the medial nucleus of the solitary tract. This widespread distribution of neurokinin B in the cat brainstem suggests that the neuropeptide could be involved in many different physiological functions. In comparison with previous studies carried out in the rat brainstem on the distribution of neurokinin B, our results point to a more widespread distribution of this neuropeptide in the cat brainstem.

Mapping of tachykinins in the cat spinal cord.

Using an indirect immunoperoxidase technique, the location of cell bodies and fibers containing substance P, neurokinin A and neurokinin B was studied in the cat spinal cord. The former two neuropeptides showed a widespread distribution throughout the whole spinal cord, whereas the distribution of neurokinin B was more restricted. Neurokinin A-immunoreactive structures showed a more widespread distribution and a higher density than the immunoreactive structures observed to contain substance P. In the cat spinal cord, we observed cell bodies containing neurokinin A, but no cell bodies containing neurokinin B or substance P were found. These cell bodies were located in laminae V (sacral 1 and 2 levels), VI (sacral 1 and 3), VII (lumbar 7, sacral 1 and 3, caudal 1) and X (sacral 1). Laminae I and II showed the highest density of immunoreactive fibers for each of the three tachykinins studied, being in general lamina IV who showed the lowest number of immunoreactive fibers containing substance P, neurokinin A or B. The anatomical distribution of the three tachykinins studied in the cat spinal cord indicates that the neuropeptides could be involved in the neurotransmission and/or in the neuromodulation of nociceptive information, as well as in autonomic and affective responses to pain. Moreover, the involvement of substance P, neurokinin A or B in other functions unrelated to the transmission of pain is also possible (autonomic and motor functions). The distribution of the neuropeptides studied in the cat is compared with the location of the same neuropeptides in the spinal cord of other species. The possible origin of the tachykinergic fibers in the cat spinal cord is also discussed.

An immunocytochemical mapping of ACTH/CLIP in the cat diencephalon.

Using an indirect immunoperoxidase technique, the location of cell bodies and fibres containing adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide (ACTH/CLIP) was studied in the cat diencephalon. Immunoreactivity was observed in several diencephalic nuclei of the cat in which no immunoreactivity has been previously reported. In this sense, a low density of immunoreactive cell bodies was found in the nucleus ventromedialis hypothalami; a high density of immunoreactive fibres was found in the medial preoptic area; a moderate density in the lateral preoptic area and in the nuclei centralis thalami (pars medialis), interventralis thalami, interanteromedialis thalami, parafascicularis and praemamillaris (pars ventralis and pars dorsalis); a low density in the nuclei habenularis lateralis and reuniens thalami, and single fibres were found in the nuclei lateralis thalami (pars anterior), habenularis medialis, parataenialis, corpus geniculatum mediale, ventralis thalami (pars medialis) and in the fornix. Our results point to a more widespread distribution of ACTH/CLIP immunoreactive structures in the cat diencephalon in comparison with previous studies carried out in the same region of this feline.

5-HT1A receptor activation before acute stress counteracted the induced long-term behavioral effects.

The long-term behavioral consequences of acute immobilization (IMMO) in rats and the effects of 5-HT(1A) receptor activation (8-OH-DPAT: 0.3 mg/kg, sc) were studied. Corticosterone levels after IMMO with previous 8-OH-DPAT treatment were also studied. Twenty-four hours after IMMO (3 h), rats performed conditioned (passive avoidance) and unconditioned (escape behavior) anxiety tests in the elevated T maze. Pre-exposure to IMMO induces long-term behavioral changes in contrast with control rats. These behavioral alterations include an increase of anxiogenic responses, such as exploratory behavior and passive avoidance response. This effect was counteracted by 8-OH-DPAT pretreatment and reversed by WAY-100635 when administered before 8-OH-DPAT. Serum corticosterone levels increased during the first hour of stress and after 8-OH-DPAT administration. Our results support the hypothesis that involvement of acute stress is crucial in the anxiety-like behaviors and in the potentiation of fear. The activation of 5-HT(1A) receptors counteracted the long-term effects induced by IMMO.

Group I mGluR antagonist AIDA protects nigral DA cells from MPTP-induced injury.

The effects of i.c.v. injection of AIDA, a group I mGluR antagonist, were studied on the nigral DA cells after MPTP-induced injury in the black mouse, using TH immunocytochemistry and unbiased stereology. MPTP reduced the total number of TH-IR neurons by 55.2% and non-TH-IR neurons by 27.5%. A 15 min AIDA pre-treatment (10 nmol) selectively counteracted the loss of TH-IR cells caused by MPTP as evaluated 10 days after the insult without changing the total number of non-neuronal cell nuclei. The results suggest that group I mGluR antagonists may have a neuroprotective role against MPTP-induced degeneration of DA neurons and thus probably also against neurodegenerative processes occurring in Parkinson's disease.

Pharmacokinetics of oral nifedipine in different populations.

Nifedipine disposition varies among populations. Reports on oral nifedipine pharmacokinetics show that peak plasma levels and AUC values are higher in Mexican and Japanese than in European and North American subjects. Increased nifedipine bioavailability in the nonwhite populations is likely due to nutritional habits. Certain flavonoids that inhibit the first-pass metabolism of dihydropyridines are present in the diets of both Mexican and Japanese. Differences in phenotypes may play a role in interethnic variability.

Bioavailability of oral cyclosporine in healthy Mexican volunteers: evidence for interethnic variability.

The existence of population variations in cyclosporine pharmacokinetics could be expected, as this drug, similar to nifedipine, is biotransformed by cytochrome P-450 subfamily 3A4, and the existence of interethnic variability in nifedipine disposition has been demonstrated previously. The bioavailability of oral cyclosporine was studied in 23 healthy Mexican volunteers receiving 7.5-mg/kg doses of cyclosporine. Blood samples were drawn over 24 hours, and concentration of cyclosporine in whole blood was determined by a radioimmunoassay using monoclonal antibodies specific for the unchanged drug. The bioavailability of cyclosporine exhibited wide interindividual variability. Maximum concentration (Cmax) ranged from 528 ng/mL to 2,689 ng/mL, area under the concentration-time curve (AUC) ranged from 6,550 ng.hr/mL to 18,562 ng.hr/mL, and time to reach Cmax (tmax) ranged from 1 to 8 hours. Half-life (t1/2) exhibited less important variations, ranging from 4.4 to 9.1 hours. The bioavailability of oral cyclosporine in Mexicans was higher than that reported for white populations under similar conditions. The present results suggest the existence of interethnic variability in the pharmacokinetics of cyclosporine, as is the case with nifedipine.

Alpha-neo-endorphin-like immunoreactivity in the cat brain stem.

This paper examines the distribution of fibers and cell bodies containing alpha-neo-endorphin in the cat brain stem by using an indirect immunoperoxidase technique. A high or moderate density of immunoreactive cell bodies was found in the superior central nucleus, nucleus incertus, dorsal tegmental nucleus, nucleus of the trapezoid body, and in the laminar spinal trigeminal nucleus, whereas a low density of such perikarya was observed in the inferior colliculus, nucleus praepositus hypoglossi, dorsal nucleus of the raphe, nucleus of the brachium of the inferior colliculus, and in the nucleus of the solitary tract. The highest density of immunoreactive fibers was found in the substantia nigra, dorsal motor nucleus of the vagus, nucleus coeruleus, lateral tegmental field, marginal nucleus of the brachium conjunctivum, and in the inferior and medial vestibular nuclei. These results indicate that alpha-neo-endorphin is widely distributed in the cat brain stem and suggest that the peptide could play an important role in several physiological functions, e.g., those involved in respiratory, cardiovascular, auditory, and motor mechanisms.

Neurotensin-like immunoreactivity in the diencephalon of the adult male cat.

Using an indirect immunoperoxidase technique, the location of neurotensin-like fibers and cell bodies was studied in the diencephalon of the cat. The findings showed that the hypothalamus is richer in neurotensin-like-immunoreactive structures than the thalamus, and that neurotensin-like-immunoreactive structures are more widely distributed in the hypothalamus than in the thalamus. A high density of immunoreactive fibers was observed in the hypothalamic regions, area hypothalamica dorsalis, hypothalamus posterior, nucleus (n.) filiformis and n. arcuatus, whereas a moderate density was found in the n. parafascicularis, n. paraventricularis anterior, hypothalamus lateralis, median eminence and n. paraventricularis hypothalami. Other diencephalic regions such as n. lateralis posterior, n. lateralis dorsalis, n. medialis dorsalis, n. habenularis lateralis, n. centrum medianum, n. rhomboidens, n. reuniens, hypothalamus anterior, n. supra chiasmaticus, hypothalamus ventromedialis, n. supraopticus and hypothalamus dorsomedialis had the lowest density of immunoreactive fibers. In addition, the densest clusters of neurotensin-like perikarya were found in the n. arcuatus, n. centralis medialis and hypothalamus posterior, whereas the n. medialis dorsalis, n. paraventricularis anterior, n. reuniens, hypothalamus lateralis and hypothalamus ventromedialis had the lowest density. In the n. lateralis dorsalis, n. supraopticus, area hypothalamica dorsalis and n. supra chiasmaticus the density of immunoreactive perikarya was moderate.

Distribution of neurotensin-like immunoreactive cell bodies and fibers in the brainstem of the adult male cat.

We studied the distribution of cell bodies and fibers containing neurotensin in the brainstem of the cat using an indirect immunoperoxidase technique. A high or moderate density of immunoreactive perikarya was found in the interpeduncular nucleus, inferior colliculus, nucleus of the brachium of the inferior colliculus and in the lateral tegmental field. Moreover, a high density of neurotensin-immunoreactive fibers was observed in the periaqueductal gray, locus coeruleus and in the marginal nucleus of the brachium conjunctivum. The interpeduncular nucleus, nucleus of the solitary tract and the dorsal motor nucleus of the vagus contained a moderate density of immunoreactive fibers.

Mapping of alpha-melanocyte-stimulating hormone-like immunoreactivity in the cat diencephalon.

Using an indirect immunoperoxidase technique, we studied the location of alpha-melanocyte-stimulating hormone-like fibers and cell bodies in the cat diencephalon. In the thalamus, almost all the immunoreactive fibers were found in the midline region, whereas in the hypothalamus immunoreactive fibers were observed in the whole structure. The hypothalamus showed a higher density of both immunoreactive fibers and cell bodies; no immunoreactive neurons were found in the thalamus. The densest network of immunoreactive fibers was observed in the epithalamus (nucleus periventricularis anterior) and in the hypothalamic nuclei filiformis, hypothalami ventromedialis, arcuatus, periventricularis hypothalami, area hypothalamica dorsalis, and hypothalamus posterior. A high density of immunoreactive neurons was found in the nucleus arcuatus, in the hypothalamus lateralis, and in the area hypothalamica dorsalis; a low density was found in the nucleus hypothalami ventromedialis and in the hypothalamus dorsomedialis. By comparison with the studies of previous researchers, these data showed a more widespread distribution of alpha-melanocyte-stimulating hormone-like immunoreactive fibers and perikarya in the feline hypothalamus. Moreover, our findings indicate that the peptide is widely distributed in the cat diencephalon, suggesting that alpha-melanocyte-stimulating hormone might be involved in several physiological functions.

ACTH/CLIP immunoreactivity in the cat brain stem.

The distribution of adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide was studied in the cat brain stem, using an indirect immunoperoxidase technique. No immunoreactive cell bodies were observed. However, a high density of immunoreactive fibers was found in the periaqueductal gray, the dorsal nucleus of the raphe, the locus coeruleus, and the marginal nucleus of the brachium conjunctivum. A moderate density was found in the central linear nucleus, the central tegmental field, the Kolliker-Fuse nucleus, the inferior central nucleus, and the postpyramidal nucleus of the raphe. A low density was found in the superior and inferior colliculi, the interpeduncular nucleus, the nucleus sagulum, the superior central nucleus, the cuneiform nucleus, the accessory dorsal tegmental nucleus, the nucleus of the solitary tract, the dorsal motor nucleus of the vagus, and the paralemniscal, magnocellular, gigantocellular, and lateral tegmental fields. Moreover, single immunoreactive fibers were observed in numerous nuclei of the cat brain stem. In comparison with previous studies carried out in the same region of the cat, as well as the rat and the human, our results point to a more widespread distribution of adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide immunoreactive structures in the cat brain stem. This widespread distribution indicates that the peptide might be involved in several physiological functions of the cat brain stem.

Distribution of neuropeptide Y-like immunoreactive fibers in the cat thalamus.

Neuropeptide Y-like immunoreactivity was studied in the thalamus of the cat using an indirect immunoperoxidase method. The densest network of immunoreactive fibers was observed in the nucleus (n.) paraventricularis anterior. In the anterior, intralaminar and midline thalamic nuclei, as well as in the n. geniculatum medialis, n. geniculatum lateralis, n. habenularis lateralis, n. medialis dorsalis, n. lateralis posterior and n. pulvinar a low density of neuropeptide Y-like immunoreactive fibers was observed. Neuropeptide Y-like fibers were totally absent in the n. ventralis lateralis, n. ventralis medialis, n. ventralis postero-medialis and n. ventralis postero-lateralis. In addition, neuropeptide Y-like perikarya were found in the n. parafascicularis, n. suprageniculatus, n. geniculatum lateralis ventralis, n. medialis dorsalis and n. lateralis posterior.

Immunohistochemical mapping of enkephalins, NPY, CGRP, and GRP in the cat amygdala.

This immunohistochemical study shows a wide distribution of neuropeptides in the cat amygdala. Neuropeptide Y is present along the whole amygdaloid complex, and fibers and cell bodies containing neuropeptide Y are observed in all the nuclei studied. Leucine-enkephalin-, gastrin-releasing peptide/bombesin-, and calcitonin gene-related peptide-immunoreactive fibers and perikarya are observed only in discrete nuclei of the amygdaloid complex, whereas only fibers -but no cell bodies- containing methionine-enkephalin-Arg6-Gly7-Leu8 have been observed. No immunoreactivity has been found for gamma-melanocyte-stimulating hormone, dynorphin A (1-17), or galanin. These data are compared with those reported in the amygdala of other mammals.

Somatostatin-28 (1-12)-like immunoreactivity in the cat diencephalon.

Using an indirect immunoperoxidase technique, the location of somatostatin-28 (1-12)-like immunoreactive fibres and cell bodies in the cat diencephalon was studied. The hypothalamus was richer in somatostatin-28 (1-12)-like immunoreactive structures than the thalamus. A high density of immunoreactive fibres was observed in the nuclei habenularis lateralis, paraventricularis anterior (its caudal part), filiformis, hypothalami ventromedialis, and regio praeoptica, whereas a moderate density was found in the nuclei paracentralis, supraopticus, supra chiasmaticus, hypothalamus posterior and area hypothalamica dorsalis. The nuclei lateralis dorsalis, lateralis posterior, medialis dorsalis, rhomboidens, centralis medialis, ventralis medialis, reuniens, anterior dorsalis, parataenialis, interanteromedialis, hypothalamus lateralis, hypothalamus dorsomedialis and arcuatus had the lowest density of immunoreactive fibres. In addition, a high or moderate density of somatostatin-28 (1-12)-like immunoreactive cell bodies was observed in the nuclei paraventricularis hypothalami, supraopticus, supra chiasmaticus, area hypothalamics dorsalis, subparafascicularis, hypothalamus posterior and hypothalamus anterior, whereas scarce immunoreactive perikarya were visualized in the nuclei lateralis dorsalis and parafascicularis. The distribution of somatostatin-28 (1-12)-like immunoreactive structures is compared with the location of other neuropeptides in the cat diencephalon.

Distribution of somatostatin-28 (1-12) in the cat brainstem: an immunocytochemical study.

We studied the distribution of somatostatin-28 (1-12)-immunoreactive fibers and cell bodies in the cat brainstem. A moderate density of cell bodies containing the peptide was observed in the ventral nucleus of the lateral lemniscus, accessory dorsal tegmental nucleus, retrofacial nucleus and in the lateral reticular nucleus, whereas a low density of such perikarya was found in the interpeduncular nucleus, nucleus incertus, nucleus sagulum, gigantocellular tegmental field, nucleus of the trapezoid body, nucleus praepositus hypoglosii, lateral and magnocellular tegmental fields, nucleus of the solitary tract, nucleus ambiguous and in the nucleus intercalatus. Moreover, a moderate density of somatostatin-28 (1-12)-immunoreactive processes was found in the dorsal nucleus of the raphe, dorsal tegmental nucleus, accessory dorsal tegmental nucleus, periaqueductal gray and in the marginal nucleus of the brachium conjunctivum. Finally, few immunoreactive fibers were visualized in the interpeduncular nucleus, cuneiform nucleus, locus coeruleus, nucleus incertus, superior and inferior central nuclei, nucleus sagulum, ventral nucleus of the lateral lemniscus, nucleus praepositus hypoglosii, medial vestibular nucleus, Kölliker-Fuse area, nucleus ambiguous, retrofacial nucleus, postpyramidal nucleus of the raphe, nucleus of the solitary tract, dorsal motor nucleus of the vagus, lateral reticular nucleus and laminar and alaminar spinal trigeminal nuclei.

An immunocytochemical mapping of beta-endorphin (1-27) in the cat diencephalon.

The distribution of beta-endorphin (1-27) immunoreactive cell bodies and fibres was studied in the diencephalon of the cat using an indirect immunoperoxidase technique. In the thalamus, almost all the immunoreactive fibres were found in the midline region and in nuclei located near the midline, whereas in the hypothalamus fibres containing beta-endorphin (1-27) were visualized extending by the whole structure. The hypothalamus showed a higher density of beta-endorphin (1-27) immunoreactive fibres than the thalamus, as well as immunoreactive cell bodies, since in the thalamus no beta-endorphin (1-27) immunoreactive neuron was located. The densest network of immunoreactive fibres was observed in the epithalamus (nucleus periventricularis anterior) and in the hypothalamic nuclei arcuatus, hypothalami ventromedialis, suprachiasmaticus, periventricularis hypothalami, hypothalamus dorsomedialis, area hypothalamica dorsalis, hypothalamus anterior, filiformis, hypothalamus posterior and regio praeoptica. In the hypothalamus, a high density of perikarya containing beta-endorphin (1-27) was observed in the nucleus arcuatus and a low density in the nucleus hypothalami ventromedialis. The distribution of beta-endorphin (1-27) immunoreactive fibres and perikarya is compared with the location of other neuropeptides in the cat diencephalon. Our findings reveal that b-endorphin (1-27) immunoreactive structures are widely distributed in the cat diencephalon, suggesting that the peptide might be involved in several physiological functions.

Distribution of gastrin-releasing peptide/bombesin-like immunoreactive cell bodies and fibres in the brainstem of the cat.

Using an indirect immunoperoxidase technique, the location of gastrin-releasing/bombesin-like immunoreactive fibres and cell bodies in the cat brainstem was studied. A moderate or low density of immunoreactive cell bodies was observed in the nucleus of the brachium of the inferior colliculus, pericentral nucleus of the inferior colliculus, ventral nucleus of the lateral lemniscus and in the external division of the lateral reticular nucleus. The densest network of immunoreactive fibres was visualized in the interpeduncular nucleus, marginal nucleus of the brachium conjunctivum, alaminar and laminar spinal trigeminal nuclei and in the substantia nigra. The periaqueductal gray, brachium of the inferior colliculus, nucleus of the brachium of the inferior colliculus, locus coeruleus, nucleus incertus, Kölliker-Fuse nucleus, facial nucleus, medial nucleus of the solitary tract and the area postrema contained a moderate density of immunoreactive fibres, whereas the pericentral nucleus of the inferior colliculus, nucleus sagulum, cuneiform nucleus, dorsal nucleus of the raphe, superior central nucleus, central, lateral and paralemniscal tegmental fields, ventral nucleus of the lateral lemniscus, dorsal tegmental nucleus, postpyramidal nucleus of the raphe, nucleus ambiguus, accessory dorsal tegmental nucleus, dorsal motor nucleus of the vagus and the inferior olive had the lowest density of immunoreactive fibres.

Neurokinin A-like immunoreactivity in the cat brainstem.

We have studied the distribution of neurokinin A-like immunoreactive cell bodies and fibers in the cat brainstem. The densest clusters of perikarya containing the peptide were observed in the periaqueductal gray, inferior colliculus, postpyramidal nucleus of the raphe, medial nucleus of the solitary tract and in the lateral reticular nucleus. By contrast, the interpeduncular nucleus, magnocellular part of the red nucleus, central tegmental field, cuneiform nucleus, dorsal tegmental nucleus, nucleus sagulum and the medial and inferior vestibular nuclei had the lowest density, whereas a moderate density of immunoreactive cell bodies was found in the superior colliculus, medial division of the dorsal nucleus of the raphe, nucleus incertus, locus coeruleus and in the Kölliker-Fuse area. The highest density of immunoreactive fibers was observed in the substantia nigra, periaqueductal gray, marginal nucleus of the brachium conjunctivum, medial vestibular nucleus, medial nucleus of the solitary tract, laminar spinal trigeminal nucleus, inferior colliculus, medial division of the dorsal nucleus of the raphe, locus coeruleus, dorsal tegmental nucleus and in the spinal trigeminal tract. A moderate density of immunoreactive fibers was found in the dorsal motor nucleus of the vagus and in the postpyramidal nucleus of the raphe and a low density in the cuneiform nucleus, Kölliker-Fuse area, nucleus sagulum, inferior and superior central nuclei, lateral reticular nucleus and in the lateral and magnocellular tegmental fields.

Increased vasopressor actions of intraventricular neuropeptide Y-(13-36) in spontaneously hypertensive versus normotensive Wistar-Kyoto rats. Possible relationship to increases in Y2 receptor binding in the nucleus tractus solitarius.

The C-terminal NPY fragment (13-36)[NPY-(13-36)], a Y2 receptor agonist, elicits vasopressor responses upon central administration. The cardiovascular responses of NPY-(13-36) together with the distribution of NPY receptor subtypes within the nucleus tractus solitarius (nTS) have therefore been studied in spontaneously hypertensive rats (SHR). NPY-(13-36) was injected intracerebro-ventricularly in different doses (7.5 to 3000 pmol) in awake, unrestrained rats to evaluate the cardiovascular effects. NPY receptor subtypes were studied by autoradiography using [125I]peptide YY ([125I]PYY) as a radioligand and by masking the NPY Y1 and Y2 receptor subtypes with unlabelled [Leu31,Pro43]NPY and NPY-(13-36) respectively. In both male SHR and age-matched male normotensive Wistar-Kyoto rats (WKY) NPY-(13-36) injections elicited vasopressor effects. In WKY this effect was dose-dependent and became significant at doses from 75 pmol, whereas in the SHR the vasopressor effect had a longer duration than in the WKY and became significant at lower doses (25 pmol) but associated with the development of an early ceiling effect. The heart rate was unaffected in both groups of rats. Total specific [125I]PYY binding in the nTS was 25% higher in SHR than in WKY rats. By masking the Y1 and Y2 receptor subtypes respectively it could be shown that this difference was due to an increase in Y2 receptor binding within the nTS. The present results give evidence for an increased potency but not an increased efficacy of NPY-(13-36) in inducing a pressor response in the SHR associated with a longer duration as compared with the WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)