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Biomedical subjects

J Hannibal

Publications and source records attributed to J Hannibal.

At least 37 records · Page 2Linked to original sources
PubMed1999

PACAP gene expression in neurons of the rat hypothalamo-pituitary-adrenocortical axis is induced by endotoxin and interleukin-1beta.

Inflammatory stress due to infection by various micro-organisms is known to activate the hypothalamo-pituitary-adrenocortical (HPA) axis through inflammatory mediators. Recently, pituitary-adenylate-cyclase-activating polypeptide (PACAP) was shown to be located in corticotropin-releasing factor containing neurons of the medial parvocellular part of the hypothalamic paraventricular nucleus (mpPVN). In the present study, we demonstrate that PACAP gene expression is induced in neurons of the mpPVN after intraperitoneal administration of bacterial lipopolysaccharide (LPS) which was accompanied by a marked increase in PACAP immunoreactivity in the external zone of the median eminence. As determined by quantitative in situ hybridization, PACAP gene expression was rapidly induced after 4 h and was elevated for 48 h, declining to normal levels after 72 h. A significant increase in PACAP mRNA was also observed following intraperitoneal injection of interleukin-1beta. PACAP gene expression was not induced by LPS in vagotomized animals, suggesting that the increase in PACAP mRNA following immune activation by LPS is mediated via the vagus nerve. The findings suggest that PACAP may function as a hypothalamo-pituitary-releasing factor during acute inflammation.

Animals↗
PubMed1999

Pituitary adenylate cyclase-activating polypeptide is an auto/paracrine stimulator of acute progesterone accumulation and subsequent luteinization in cultured periovulatory granulosa/lutein cells.

Recently, we have demonstrated that pituitary adenylate cyclase-activating polypeptide (PACAP) is transiently expressed in steroidogenic ovarian cells during the periovulatory period. This prompted us to establish an in vitro system in which the potential local regulatory role of PACAP during periovulatory progesterone production could be examined. Granulosa/lutein cells from PMSG- and human CG (hCG)-stimulated immature rats were used. The cells were isolated from preovulatory follicles 4-6 h after the hCG injection, at which time the transient ovarian PACAP expression begins in vivo. By immunocytochemistry on intact cells and RIA on cell extracts and culture medium, granulosa/lutein cells were found to accumulate and secrete PACAP during incubation. Furthermore, the cells responded to exogenous PACAP 38 with a rapid (10(-7) M induced a peak value 20-fold higher than controls at 2 h) and dose-dependent accumulation of progesterone. PACAP 38 (5 x 10(-9) M), in combination with an approximately half-maximal dose of hCG (1 ng/ml), showed an additive effect on progesterone accumulation. Immunoneutralization of endogenously released PACAP was performed using the IgG fraction from a specific PACAP antiserum that dose-dependently inhibits the progesterone accumulating effect of exogenous PACAP 38. The acute effects of endogenously released PACAP were studied during 8 h of incubation of granulosa/lutein cells with anti-PACAP IgG (100 microg/ml). A significant reduction in progesterone accumulation was observed after 4, 6, and 8 h [38.7% (P < 0.05), 41.2% (P < 0.02), and 50% (P < 0.002), respectively], compared with nonimmune IgG (100 microg/ml) treated cultures. The long-term effects on luteinization induced by endogenously released PACAP were studied after incubation of the cells with anti-PACAP IgG or nonimmune IgG for 24 h, followed by incubation for 9 days in serum-containing medium. Under these conditions, nonimmune IgG-treated cells assumed a luteal phenotype, accumulating large and stable amounts of progesterone and acquiring hypertrophic cell bodies with numerous lipid droplets and distinct nucleoli in the large nuclei. Anti-PACAP IgG-treated cells displayed morphological and functional signs of impaired luteinization being smaller and more irregular and with progesterone accumulation being significantly lower throughout the incubation period [56.4% (P < 0.02), 69.2% (P < 0.05), 43.8% (P < 0.02), and 52.2% (P < 0.02) at 1, 4, 7, and 10 days, respectively]. Together, these findings support an auto- or paracrine role for PACAP during gonadotropin-induced acute periovulatory progesterone production and subsequent luteinization in granulosa/lutein cells.

Animals↗
PubMed1998

Pituitary adenylate cyclase activating peptide (PACAP) in the retinohypothalamic tract: a daytime regulator of the biological clock.

The retinohypothalamic tract (RHT) relays photic information from the eyes to the brain biological clock in the suprachiasmatic nucleus (SCN). Activation of this pathway by light plays a role in adjusting circadian timing to light exposure at night. Here we report a new signaling pathway by which the RHT regulates circadian timing in the daytime as well. Using dual-immunocytochemistry for PACAP and the in vivo tracer Cholera toxin subunit B (ChB), intense PACAP immunoreactivity (PACAP-IR) was observed in retinal afferents at the rat SCN as well as in the intergeniculate leaflet (IGL) of the thalamus. This PACAP-IR was nearly lost upon bilateral eye enucleation. PACAP afferents originated from ganglion cells distributed throughout the retina. The phase of circadian rhythm measured as SCN neuronal activity in vitro was significantly advanced by application of PACAP-38 during the subjective day, but not at night. The effect is channelled to the clock via a PACAP 1 receptor-cAMP signaling mechanism. Thus, in addition to its role in nocturnal regulation by glutamatergic neurotransmission, the RHT can adjust the biological clock by a PACAP-cAMP-dependent mechanism during the daytime.

Animals↗
PubMed1998

Expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the postnatal and adult rat cerebellar cortex.

In adult rat, immunostaining for pituitary adenylate cyclase activating polypeptide (PACAP) was demonstrated in the soma and dendrites of Purkinje cells and in nerve fibres around granule cells. PACAP in the Purkinje cells was confirmed by the presence of mRNA. The concentration of PACAP-38 was high after birth and declined to adult levels within a few weeks. At birth PACAP-immunoreactive nerve fibres and a few cells were present in the Purkinje cell layer, but already at postnatal day 7 an adult PACAP immunostaining pattern was found. The findings suggest that PACAP could be a neurotransmitter in the adult cerebellum and provide a morphological correlate for the reported in vitro anti-apoptotic PACAP effects on cerebellar granule cells from 1-week-old rats.

Animals↗
PubMed1998

PACAP and PACAP receptors in insulin producing tissues: localization and effects.

We have studied the localization, receptor occupancy and potency of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in insulin-producing tissues. Immunocytochemistry showed that PACAP-like immunoreactivity (PACAP-IR) was localized to pancreatic nerves with accumulation in intrapancreatic ganglia in both mouse and rat. In contrast, PACAP-IR could not be demonstrated in endocrine cells. Furthermore, in situ hybridization, using oligodeoxyribonucleotide probes recognizing mRNA for PACAP receptors, demonstrated that mouse and rat pancreas, and the insulinoma cell lines HIT-T15 and RINm5F, expressed both the PACAP type 1 and the VIP2/PACAP receptors. Moreover, both PACAP27 and PACAP38 dose-dependently (0.1 nM to 100 nM) and equipotently stimulated insulin secretion in isolated mouse and rat islets and in HIT-T15 and RINm5F cells. Furthermore, in mouse islets, vasoactive intestinal polypeptide (VIP) was of equal potency as PACAP at stimulating insulin secretion. In mouse, PACAP also stimulated insulin secretion in a subfraction of the isolated islets also at the low dose of 1 fM. Thus, (1) PACAP is exclusively a neuropeptide in the pancreas, (2) insulin-producing cells express PACAP type 1 and VIP2/PACAP receptors and (3) the two forms of PACAP equipotently stimulate insulin secretion. Based on these results, we suggest that PACAP is involved in the neural regulation of insulin secretion.

Animals↗
PubMed1998

Embryonic expression of pituitary adenylate cyclase-activating polypeptide in sensory and autonomic ganglia and in spinal cord of the rat.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that is related structurally to vasoactive intestinal polypeptide (VIP), has been shown to stimulate neuronal growth and differentiation, indicating a possible function in the development of the nervous system. Studies have indicated that the PACAP receptor is expressed during development, but data on PACAP expression are limited mainly to postnatal development. In the present study, we used immunohistochemistry and in situ hybridization histochemistry to examine the expression of PACAP in autonomic and sensory ganglia and spinal cord of rat fetuses at embryonic days 12-21 (E12-E21). PACAP immunoreactivity was visualized by using a specific monoclonal anti-PACAP antibody to detect both PACAP-38 and PACAP-27, and PACAP mRNA was visualized by using a [33P]-labeled cRNA-probe. PACAP- nerve fibers were observed in the spinal cord as early as E13. At E14, PACAP-immunoreactive nerve fibers projected to the sympathetic trunk, where few PACAP- nerve cell bodies were seen from E15. On the same embryonic day, PACAP-immunoreactive nerve cell bodies appeared in the intermediolateral column of the spinal cord. From E15 to E16, PACAP-immunoreactive nerve cell bodies were visible within sensory and autonomic ganglia, such as the dorsal root, the trigeminal, the sphenopalatine, the otic, the submandibular, and the nodose ganglia. At E16, PACAP+ nerve fibers were innervating the adrenal medulla, and immunoreactive fibers could also be observed in the superior cervical ganglion, in which PACAP-immunoreactive cell bodies were detected occasionally from E18. The synthesis of PACAP in neuronal cell bodies was confirmed by the demonstration of PACAP mRNA with in situ hybridization histochemistry. Thus, in all of the structures examined, PACAP appeared at roughly the same embryonic stage and, thereafter, increased to the adult level before birth. Because PACAP occurred with the same distribution pattern as that described in the adult rat, there is no evidence for transient expression. The early expression of PACAP suggests a possible role for the peptide in the developing nervous system.

Adrenal Glands↗
PubMed1998

Pituitary adenylate cyclase-activating polypeptide-nerve terminals densely innervate corticotropin-releasing hormone-neurons in the hypothalamic paraventricular nucleus of the rat.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in many regions of the hypothalamus including the paraventricular nucleus (PVN). In this study, using well-characterized antibodies against PACAP and corticotropin-releasing hormone (CRH), we identified numerous nerve fibers with PACAP-immunoreactivity (ir) closely apposed to CRH neurons in the medial parvocellular subdivision of the rat PVN. Electron microscopy revealed the presence of synapses between PACAP-ir containing terminals and CRH-perikarya and -dendrites. These morphological observations suggest that PACAP may modulate the activation of the hypothalamic-pituitary-adrenal axis.

Adrenalectomy↗
PubMed1998

Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: distribution and effects of capsaicin or denervation.

The expression of pituitary adenylate cyclase activating polypeptide (PACAP) was studied in the gastrointestinal tract (GI-tract) of normal rats using radioimmunoassay, chromatography, immunocytochemistry, and in situ hybridization. PACAP-38, PACAP-27, and PACAP-related peptide were demonstrated in all parts of the GI-tract, PACAP-38 being the predominant form confirmed by chromatography. PACAP-immunoreactive nerve fibers and nerve cell bodies were found in the myenteric ganglia throughout the GI-tract. PACAP-containing nerve cell bodies were also demonstrated in the submucous ganglia of the small and large intestine. The synthesis of PACAP in intrinsic neurons was confirmed by in situ hybridization. Double immunostaining showed that PACAP is present in calcitonin gene-related peptide-containing sensory nerve fibers as well as in vasoactive intestinal polypeptide (VIP)- or VIP/gastrin-releasing peptide (GRP)-containing (intramural) nerve fibers in the upper GI-tract and in anally projecting, intrinsic VIP-and VIP/nitric oxide syntase-containing nerve cell bodies and nerve fibers in the small and large intestine. Neonatal treatment with capsaicin significantly reduced the concentration of PACAP-38 in the esophagus, stomach, and colon. Extrinsic denervation decreased the PACAP-38 concentration in the stomach, while no change was observed in the small intestine. These results indicate that PACAP- immunoreactive nerve fibers in the GI-tract originate from both intrinsic (enteric) and extrinsic (presumably sensory) sources suggesting that PACAP may have diverse gastrointestinal functions.

Animals↗
PubMed1998

Pituitary adenylate cyclase activating polypeptide immunoreactivity in capsaicin-sensitive nerve fibres supplying the rat urinary tract.

Pituitary adenylate cyclase activating peptide is a new member of the vasoactive intestinal polypeptide family of peptides which is present in the brain as well as neuronal elements of a number of peripheral organs. Pituitary adenylate cyclase activating peptide occurs in two forms, pituitary adenylate cyclase activating peptide-38 and the C-terminally truncated 27 amino acid form, pituitary adenylate cyclase activating peptide-27, both derived from the same precursor which in addition gives rise to a structurally-related peptide, pituitary adenylate cyclase activating peptide-related peptide. Using specific radioimmunoassays for pituitary adenylate cyclase activating peptide-38, pituitary adenylate cyclase activating peptide-27 and pituitary adenylate cyclase activating peptide-related peptide we found that all three pituitary adenylate cyclase activating peptide-precursor-derived peptides were present in tissue extracts from the ureter, the urinary bladder and the urethra. Pituitary adenylate cyclase activating peptide-38 was the dominating peptide with the highest concentration in the ureter. When extracts from the urinary bladder were fractionated by reverse phase high pressure liquid chromatography immunoreactive components corresponding to synthetic pituitary adenylate cyclase activating peptide-38, pituitary adenylate cyclase activating peptide-27 and pituitary adenylate cyclase activating peptide-related peptide were identified with the respective antisera. By immunohistochemistry, using a specific monoclonal mouse anti-pituitary adenylate cyclase activating peptide antibody, pituitary adenylate cyclase activating peptide-immunoreactivity was shown to have a widespread distribution in the rat urinary tract, localized exclusively to nerve fibres. No immunoreactive neuronal cell bodies were observed in any of the tissues. Pituitary adenylate cyclase activating peptide was shown to be located in varicose nerve fibres associated with blood vessels and smooth muscle. The majority of pituitary adenylate cyclase activating peptide-positive nerve fibres and bundles were, however, present in subepithelial plexuses from which delicate varicose nerve fibres entered the urothelium. Double immunostaining for pituitary adenylate cyclase activating peptide and a marker for sensory neurons, calcitonin-gene related peptide, disclosed that the two peptides were almost completely co-localized while the co-existence between pituitary adenylate cyclase activating peptide and the structurally related peptide vasoactive intestinal polypeptide, was scarce. Neonatal capsaicin-treatment caused a marked reduction in the concentration of immunoreactive pituitary adenylate cyclase activating peptide in all regions of the rat urinary tract, being most prominent in the ureter. By immunohistochemistry it was shown that the sensory neurotoxin caused a reduction in the number and intensity of pituitary adenylate cyclase activating peptide-immunoreactive nerve fibres in all organs of the urinary tract which was most prominent in the epithelial and subepithelial layers. Identical changes were observed for the calcitonin-gene related peptide-containing nerve fibres, while vasoactive intestinal polypeptide-positive nerve fibres were unaffected by capsaicin-treatment. In conclusion pituitary adenylate cyclase activating peptide is present in the rat urinary tract mainly in the form of pituitary adenylate cyclase activating peptide-38. Immunoreactive nerve fibres were associated with the epithelium, blood vessels and smooth musculature. Pituitary adenylate cyclase activating peptide was almost completely co-localized with calcitonin-gene related peptide and by neonatal capsaicin treatment the two peptides were identically affected. The findings suggest that pituitary adenylate cyclase activating peptide is a sensory neurotransmitter in the rat urinary tract.

Animals↗
PubMed1997

The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion.

The effects of axotomy, chemical sympathectomy and preganglionic denervation on the expression of the neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), galanin (GAL), and the PACAP type 1 receptor in the rat superior cervical ganglion (SCG) were investigated by immunocytochemistry, in situ hybridization and receptor autoradiography. An antibody recognizing the rat vesicular acetylcholine transporter (VAChT) was used for the detection of preganglionic cholinergic fibers. In the normal SCG, PACAP-immunoreactivity (-IR) was present in numerous, basket-forming, preganglionic nerve fibers, while very few SCG neurons expressed PACAP. GAL-IR was restricted to occasional neurons, and a few nerve fibers, most of which were, in addition, PACAP-IR. PACAP type 1 receptors were expressed in all nerve cell bodies. Axotomy resulted in a rapid and prominent upregulation of PACAP in a large number of nerve cell bodies. There was a large increase also in GAL expression in many nerve cell bodies. In contrast, there was a marked decline in PACAP type 1 receptor expression. Chemical sympathectomy by administration of the catcholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), gave rise to similar changes. Preganglionic denervation led to the disappearance of PACAP- and VAChT-IR baskets and to the upregulation of PACAP and GAL expression in neurons located close to the entrance of the sympathetic chain, whereas PACAP type 1 receptor expression was not affected. PACAP and GAL were coexpressed in most neurons after axotomy and chemical sympathectomy. Taken together, these results indicate that disruption of target contact and/or the infliction of an injury to the axons of the sympathetic neurons, rather than the preganglionic output, regulates the expression of PACAP, GAL and the PACAP type 1 receptor.

Animals↗
PubMed1997

Pituitary adenylate cyclase-activating peptide (PACAP) and PACAP type 1 receptor expression in regenerating adult mouse and rat superior cervical ganglia in vitro.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a regulatory peptide belonging to the vasoactive intestinal peptide (VIP) family, is widely distributed in the central and peripheral nervous system. Recent studies have shown that PACAP expression is upregulated in sensory neurons in response to axonal injury. Here we report that PACAP and PACAP type 1 receptors are located in rat and mouse superior cervical ganglia (SCG). PACAP-immunoreactivity (-IR) was demonstrated in preganglionic fibers, whereas only occasional PACAP-IR cell bodies could be observed. In situ hybridization histochemistry using 35S-labeled deoxyribonucleotide probes confirmed that PACAP mRNA was present only in occasional cell bodies. In contrast, PACAP type 1 receptor mRNA was expressed in virtually all cell bodies within the ganglia. After removal and culturing of the SCG for 24 h, there was a marked increase in PACAP mRNA, whilst PACAP type 1 receptor mRNA expression appeared to be downregulated in most nerve cell bodies except for a few scattered neurons displaying a strong upregulation. The total specific binding of PACAP to isolated SCG membranes as assayed by [125I]PACAP-27 binding showed an increase in SCG cultured for 48 h. PACAP-27 neither affected axonal outgrowth from the cultured SCG nor the survival of cells within the SCG. We conclude that PACAP and PACAP receptors are rapidly upregulated in sympathetic ganglia in response to axonal injury and that PACAP may play a role during nerve regeneration.

Animals↗
PubMed1997

Pituitary adenylate cyclase-activating peptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock.

The retinohypothalamic tract (RHT) relays photic information from the eyes to the suprachiasmatic nucleus (SCN). Activation of this pathway by light plays a role in adjusting circadian timing via a glutamatergic pathway at night. Here we report a new signaling pathway by which the RHT may regulate circadian timing in the daytime as well. We used dual immunocytochemistry for pituitary adenylate cyclase-activating peptide (PACAP) and the in vivo tracer cholera toxin subunit B and observed intense PACAP-immunoreactivity (PACAP-IR) in retinal afferents in the rat SCN as well as in the intergeniculate leaflet (IGL) of the thalamus. This PACAP-IR in the SCN as well as in the IGL was nearly lost after bilateral eye enucleation. PACAP afferents originated from small ganglion cells distributed throughout the retina. The phase of circadian rhythm measured as SCN neuronal activity in vitro was significantly advanced (3.5 +/- 0.4 hr) by application of 1 x 10(-6) M PACAP-38 during the subjective day [circadian time (CT)-6] but not at night (CT14 and CT19). The phase-shifting effect is channeled to the clock via a PACAP-R1 receptor, because mRNA from this receptor was demonstrated in the ventral SCN by in situ hybridization. Furthermore, vasoactive intestinal peptide was nearly 1000-fold less potent in stimulating a phase advance at CT6. The signaling mechanism was through a cAMP-dependent pathway, which could be blocked by a specific cAMP antagonist, Rp-cAMPS. Thus, in addition to its role in nocturnal regulation by glutamatergic neurotransmission, the RHT may adjust the biological clock by a PACAP/cAMP-dependent mechanism during the daytime.

Animals↗
PubMed1997

Immunocytochemical demonstration of pituitary adenylate cyclase activating polypeptide (PACAP) in the porcine epiphyseal cartilage canals.

Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family, is known to be a powerful stimulator of adenylate cyclase. Recently, PACAP has been shown to stimulate cAMP in osteoblast-like cells and mouse calvarian bones. In the present study, PACAP immunoreactivity (IR) was demonstrated in cartilage canals from newborn and 3-4-week-old pigs. In tissues from the femoral head and the patella with and without ossification centres, PACAP-IR nerve fibres were found in the cartilage canals innervating blood vessels. The pattern of distribution was not dependent on age or the occurrence of an ossification centre. Co-localization studies showed a high degree of co-localization with calcitonin gene-related peptide (CGRP) and substance P (SP) but little co-localization with VIP. Our findings support earlier findings of CGRP, SP and VIP in bone tissue and add PACAP to the group of neuropeptides with a sensory and/or modulatory function in bone tissue.

Animals↗
PubMed1997

Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in the mesencephalic trigeminal nucleus of the rat after transsection of the masseteric nerve.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the VIP (vasoactive intestinal polypeptide) family of peptides, has been demonstrated in neurons of the sensory system. PACAP expression of these neurons is sensitive to nerve damages such as nerve crush or axotomy. In the present study, PACAP expression in the mesencephalic trigeminal nucleus of the rat was examined after transsection of the main trunk of the masseteric nerve. The primary sensory neurons of the nucleus are considered to have purely proprioceptive functions. By quantitative in situ hybridization using a PACAP [35S]cRNA probe, an increase in PACAP mRNA was observed on the side ipsilateral to transsection already after 3 h and the expression reached a peak 24 h after surgery after which the levels gradually decreased during the next 14 days. A low and constant expression of PACAP mRNA could be seen on the side contralateral to transsection. PACAP immunoreactivity was demonstrated on the ipsilateral side after 18 h, using a specific monoclonal PACAP antibody. Co-existence of PACAP with NPY and galanin was demonstrated 7 days after transsection. Analysis of the masseteric nerve by radioimmunoassay on transsected and normal nerve stumps revealed an increase of PACAP-38 immunoreactivity in the nerve proximal to the transsection compared to the normal side (15.3 vs. 6.1 pmol/g wt). The results suggest that PACAP has a role in the early phase of adaptation to nerve injury in the proprioceptive neurons.

Animals↗
PubMed1997

Association between pituitary adenylate cyclase-activating polypeptide and thyrotropin-releasing hormone in the rat hypothalamus.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the hypothalamus including the paraventricular nucleus (PVN). In this study the anatomical relationship between PACAP- and thyrotropin-releasing hormone (TRH)-immunoreactive neuronal elements was investigated in the rat hypothalamus. Using a well-characterized mouse monoclonal antibody against PACAP and a rabbit polyclonal antiserum against TRH, we found numerous nerve fibers with PACAP-immunoreactivity (ir) closely apposed to TRH neurons in the PVN suggesting synaptic contacts. Electron microscopy confirmed the presence of synapses between PACAP-ir terminals and TRH-ir perikarya and various dendritic profiles as well as between PACAP-ir terminals and unlabeled perikarya and small- to medium-sized dendrites. Coexistence of the two peptides in perikarya of the PVN was limited to only a few neurons in the periventricular subdivision, but PACAP-ir and TRH-ir extensively coexisted in perikarya of the perifornical cell group, medial preoptic area, lateral hypothalamus and dorsomedial nucleus. The interactions between PACAP-containing neuronal processes and TRH neurons in the PVN raise the possibility that PACAP modulates the secretion of TRH destined for regulation of anterior pituitary TSH. The more general association between PACAP and TRH in other regions of the hypothalamus suggests a further role for PACAP as a cofactor in the function of TRH neurons.

Animals↗
PubMed1997

Identification of a major human high molecular weight salivary mucin (MG1) as tracheobronchial mucin MUC5B.

Human saliva contains high and low molecular weight mucin glycoproteins, that are distinct. Recently the gene encoding low molecular weight salivary mucin was cloned and designated MUC7, whereas the primary structure of high molecular weight salivary mucin is unclear. Furthermore, the expression patterns of high and low molecular weight salivary mucins in salivary glands have been debated. We have previously generated monoclonal antibodies specific for the peptide cores of salivary mucins. In the present study a monoclonal antibody specific for high molecular weight salivary mucin was used to screen a human salivary gland cDNA library. A single clone, SAL1, was identified and found to be encoded by tracheobronchial mucin gene MUC5B. A previously reported partial cDNA sequence from salivary mucin was linked to SAL1/MUC5B by genomic cloning and reverse transcriptase-polymerase chain reaction. Northern analysis of salivary gland RNA probed with SAL1 suggested that MUC5B was highly expressed in salivary glands. In situ hybridization was performed with a SAL1/MUC5B probe and a MUC7 probe. All mucous cells from the submandibular, sublingual, palatine, and labial glands labeled with the MUC5B probe, while serous cells labeled with the MUC7 probe. These findings were in accordance with our previous immunohistological results of the cellular localizations of salivary mucins. The results suggest that MUC5B is identical to or a major fraction of high molecular weight salivary mucin, and that MUC5B is expressed in all mucous cells of salivary glands. In contrast MUC7 is expressed in serous cells of salivary glands except the parotid glands.

Amino Acid Sequence↗