Innervation of the rat pineal gland by pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres

Pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres were demonstrated in the rat pineal gland. These fibres entered the pineal gland through the conarian nerve at the distal tip of the gland. A high density of the fibres was observed in the capsule of the gland, from where the immunoreactive elements penetrated into the pineal perivascular spaces and parenchyma. The majority of PACAP-immunoreactive nerve fibres also contained calcitonin gene-related peptide (CGRP). Some PACAP-immunoreactive nerve fibres contained neuropeptide Y (NPY), but only occasionally was PACAP colocalized with vasoactive intestinal peptide (VIP). After removal of both superior cervical ganglia, a high number of PACAP-containing nerve fibres were still present in the gland. In the nervous system PACAP is present in two isoforms, PACAP-38 and PACAP-27. The concentration of PACAP-38 in the superficial pineal gland was determined by radioimmunoassay to be 20.4 pmol/g tissue at midday and 18.9 pmol/g tissue at midnight. The concentration of PACAP-27 was only about 3% of the concentration of PACAP-38. In summary, this study is the first demonstration of a PACAP-containing innervation of the rat pineal gland. The PACAP concentration in the pineal gland does not exhibit a day-night difference. The colocalization of PACAP with calcitonin gene-related peptide in the pincalopetal nerve fibres indicates that the majority of PACAP-immunoreactive nerve fibres might originate from the trigeminal ganglion.     

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.     

Differential effects of VIP and PACAP on survival of cultured adult rat myenteric neurons

Our knowledge of neuroprotective factors important for the adult enteric nervous system is poor. Changes in expression of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) in enteric neurons in response to neuronal injury or colchicine treatment, as well as in intestinal adaptation, have been described. Cultured myenteric neurons increase their expression of VIP; furthermore, culturing myenteric neurons in the presence of VIP enhances neuronal survival. The aims of this study were to evaluate possible changes in PACAP expression in dissociated and cultured myenteric neurons from adult rat small intestine, and to determine the ability of PACAP-38 and PACAP-27 to promote survival of cultured myenteric neurons, as compared with that of VIP. A marked decrease in the number of surviving neurons was noted during culturing. No difference in neuronal survival was found after culturing in the presence of PACAP-38 or PACAP-27, whereas VIP significantly increased neuronal survival. In contrast to the marked increase noted in the number of VIP-expressing neurons, culturing caused no change in the number of PACAP-expressing myenteric neurons. We were thus able to demonstrate that VIP, but not PACAP, promoted survival of myenteric neurons in culture. This suggests the presence of a VIP-specific receptor mediating neuroprotection in adult myenteric neurons.     

Distribution of PACAP-38 in the central nervous system of various species determined by a novel radioimmunoassay

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two molecular forms: PACAP-38 and PACAP-27. Soon after the isolation and chemical characterization of PACAP, the first radioimmunoassay (RIA) methods have been developed, but it is a still rarely used laboratory technique in the field of PACAP research. The aim of the present study was to develop a novel, highly specific PACAP-38 assay to investigate the quantitative distribution of PACAP-38 in the central nervous system of various vertebrate species under the same technical and experimental conditions. Different areas of the brain and the spinal cord were removed from rats, chickens and fishes and the tissue samples were processed for PACAP-38 RIA. Our results indicate that the antiserum used in the RIA is C-terminal specific, without affinity for other members of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon peptide family. The average ID50 value was 48.6+/-3.4 fmol/ml determined in 10 consecutive assays. Detection limit for PACAP-38 proved to be 2 fmol/ml. PACAP-38 immunoreactivity was present in the examined brain areas of each species studied, with highest concentration in the rat diencephalons. High levels of PACAP-38 were also detected in the rat telencephalon, followed by spinal cord and brainstem. The central nervous system of the fish also contained considerable concentrations of PACAP-38, whereas lowest concentrations were measured in the central nervous system of the chicken.     

Phospholipids modulate the biophysical properties and vasoactivity of PACAP-(1--38).

The purpose of this study was to elucidate the interactions between pituitary adenylate cyclase-activating peptide (PACAP)-(1--38) and phospholipids in vitro and to determine whether these phenomena modulate, in part, the vasorelaxant effects of the peptide in the intact peripheral microcirculation. We found that the critical micellar concentration of PACAP-(1--38) was 0.4-0.9 microM. PACAP-(1--38) significantly increased the surface tension of a dipalmitoylphosphatidylcholine monolayer and underwent conformational transition from predominantly random coil in saline to alpha-helix in the presence of distearoyl-phosphatidylethanolamine-polyethylene glycol (molecular mass of 2,000 Da) sterically stabilized phospholipid micelles (SSM) (P < 0.05). Using intravital microscopy, we found that aqueous PACAP-(1--38) evoked significant concentration-dependent vasodilation in the intact hamster cheek pouch that was significantly potentiated when PACAP-(1--38) was associated with SSM (P < 0.05). The vasorelaxant effects of aqueous PACAP-(1--38) were mediated predominantly by PACAP type 1 (PAC(1)) receptors, whereas those of PACAP-(1--38) in SSM predominantly by PACAP/vasoactive intestinal peptide type 1 and 2 (VPAC(1)/VPAC(2)) receptors. Collectively, these data indicate that PACAP-(1--38) self-associates and interacts avidly with phospholipids in vitro and that these phenomena amplify peptide vasoactivity in the intact peripheral microcirculation.     

Pituitary adenylate cyclase-activating polypeptide in intrinsic and extrinsic nerves of the rat pancreas

Pituitary adenylate cyclase-activating polypeptide (PACAP) is the latest member of the vasoactive intestinal polypeptide (VIP) family of neuropeptides present in nerve fibres in many peripheral organs. Using double immunohistochemistry, with VIP as a marker for intrinsic innervation and calcitonin-gene related peptide (CGRP) as a marker for mainly extrinsic innervation, the distribution and localization of PACAP were studied in the rat pancreas. PACAP was demonstrated in nerve fibres in all compartments of the pancreas and in a subpopulation of intrapancreatic VIP-containing ganglion cells. PACAP and VIP were co-stored in intra- and interlobular nerve fibres innervating acini, blood vessels, and in nerve fibres within the islets of Langerhans. No PACAP immunoreactivity was observed in the islet cells. Another population of PACAP-immunoreactive nerve fibres co-localized with CGRP innervated ducts, blood vessels and acini. PACAP/CGRP-positive nerve fibres were also demonstrated within the islets. Neonatal capsaicin reduced the PACAP-38 concentration by approximately 50%, and accordingly a marked reduction in PACAP/CGRP-immunoreactive nerve fibres in the exocrine and endocrine pancreas was observed. Bilateral subdiaphragmatic vagotomy caused a slight but significant decrease in the PACAP-38 concentration compared with controls. In conclusion, PACAP-immunoreactive nerve fibres in the rat pancreas seem to have dual origin: extrinsic, most probably sensory fibres co-storing CGRP; and intrinsic, constituting a subpopulation of VIP-containing nerve cell bodies and fibres innervating acinar cells and islet cells. Our data provide a morphological basis for the reported effects of PACAP in the pancreas and suggest that PACAP-containing nerves in the rat pancreas may have both efferent and sensory functions.     

Pituitary adenylate cyclase activating polypeptide (PACAP) in the rat mammary gland

Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the vasoactive intestinal polypeptide (VIP) family of peptides, is present in the brain and in neuronal elements of a number of peripheral organs. Since no information on PACAP in the mammary gland exists, we have investigated, by radioimmunoassay and immunohistochemistry, the occurrence and distribution of PACAP immunoreactivity in the mammary gland of lactating and non-lactating rats. A specific monoclonal mouse anti-PACAP antibody'has been used to show that the peptide is located in nerve fibres associated with bundles of circular and longitudinal smooth muscle surrounding the lactiferous duct of the nipple. PACAP-immunoreactive nerve fibres and nerve bundles are present in the subepidermal connective tissue of the nipple and in the mammary parenchyma, some of the fibres being in close contact with blood vessels. Occasionally, a few delicate varicose fibres are associated with secretory alveoli and lactiferous ducts. The majority of PACAP-positive nerve fibres are, however, located in the glabrous skin of the nipple and the hairy skin adjacent to the nipple forming a subepithelial plexus from which delicate varicose nerve fibres enter the overlying epithelium. Double immunostaining for PACAP and a marker for sensory neurons, calcitonin gene-related peptide, has disclosed that the two peptides are almost completely co-localized. A minor population of the PACAP-immunoreactive nerve fibres shows co-existence with VIP. Although no obvious changes at the immunohistochemical level could be observed during pregnancy or lactation, elevated concentrations of immunoreactive PACAP-38 in mammary extracts have been found during lactation. Our data suggest that PACAP is involved in the nervous control of mammary gland function, probably in the transmission of suckling stimuli.     

Vascular effects of pituitary adenylate cyclase activating peptide: a comparison with vasoactive intestinal peptide

The effects of pituitary adenylate cyclase activating peptide (PACAP) on the blood pressure of the anesthetized rat and on the isolated rat tail artery were investigated and compared to those of vasoactive intestinal peptide (VIP). PACAP-38, PACAP-27 and the C-terminal fragment 16–38 caused a dose-dependent decrease in the systemic blood pressure. PACAP-27 and PACAP-38 were equipotent with VIP. The C-terminal fragment 16–38 was much less potent than VIP. The duration of action was longer for equimolar doses of PACAP-38 and PACAP-27 than for VIP and much longer than for PACAP 16–38. PACAP-27 and the phosphodiesterase inhibitor rolipram given in combination produced additive vasodepressive responses. In vitro PACAP-38, PACAP-27, VIP and PACAP 16–38 relaxed the phenylephrine-precontracted rat tail artery. PACAP-38 and PACAP-27 were equipotent with VIP. PACAP 16–38 was much less potent than the full-length peptides. The responses were resistant to atropine and propranolol. Addition of VIP 1 μM to preparations exposed to 1 μM PACAP-38 or -27 did not produce a further relaxation. VIP-like peptides, PACAP in particular, are known to activate adenylate cyclase and to elevate the plasma cyclic AMP (cAMP) concentration. cAMP was found to be a potent vasodepressor in the anaesthetized rat and a potent vasodilator of precontracted blood vessels. On the basis of these results it cannot be excluded that the vascular effects of PACAP are secondary to the effect of elevated levels of extracellular cAMP.     

Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in the cranial arteries and trigeminal sensory neurons. We therefore examined the alterations in PACAP-like immunoreactivity (PACAP-LI) in a time-dependent manner in two rat models of trigeminovascular system (TS) activation. In one group chemical stimulation (CS) was performed with i.p. nitroglycerol (NTG), and in the other one the trigeminal ganglia (TRG) were subjected to electrical stimulation (ES). The two biologically active forms, PACAP-38 and PACAP-27, were determined by means of radioimmunoassay (RIA) and mass spectrometry (MS) in the plasma, the cerebrospinal fluid (CSF), the trigeminal nucleus caudalis (TNC), the spinal cord (SC) and the TRG. The tissue concentrations of PACAP-27 were 10 times lower than those of PACAP-38 in the TNC and SC, but about half in the TRG. PACAP-38, but not PACAP-27, was present in the plasma. Neither form could be identified in the CSF. PACAP-38-LI in the plasma, SC and TRG remained unchanged after CS, but it was increased significantly in the TNC 90 and 180 min after NTG injection. In response to ES of the TRG, the level of PACAP-38 in the plasma and the TNC was significantly elevated 90 and 180 min later, but not in the SC or the TRG. The alterations in the levels of PACAP-27 in the tissue homogenates in response to both forms of stimulation were identical to those of PACAP-38. The selective increases in both forms of PACAP in the TNC suggest its important role in the central sensitization involved in migraine-like headache.     

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6-38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6-38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined.     

Presence of highly selective receptors for PACAP (pituitary adenylate cyclase activating peptide) in membranes from the rat pancreatic acinar cell line AR 4-2J

We characterized highly selective receptors for PACAP, the pituitary adenylate cyclase activating peptide, in the tumoral acinar cell line AR 4-2J derived from the rat pancreas. PACAP, a novel hypothalamic peptide related to vasoactive intestinal peptide (VIP), was tested as the full natural 38-residue peptide (PACAP-38) and as an N-terminal amidated 27-residue derivative (PACAP-27). The binding sites showed considerable affinity for [125I]PACAP-27 (Kd = 0.4 nM) and PACAP-38, while their affinity for VIP and the parent peptide helodermin was 1000-fold lower. These receptors were coupled to adenylate cyclase, the potency of PACAP-38 and PACAP-27 (Kact = 0.2 nM) being much higher than that of VIP (Kact = 100 nM) and helodermin (Kact = 30 nM). Chemical cross-linking of [125I]PACAP-27 followed by SDS-PAGE and autoradiography revealed a specifically cross-linked peptide with an Mr of 68,000 (including 3000 for one PACAP-27 molecule).     

Regulation of atrial natriuretic peptide secretion by cholinergic and PACAP neurons of the gastric antrum

Atrial natriuretic peptide (ANP) released from enterochromaffin cells helps regulate antral somatostatin secretion, but the mechanisms regulating ANP secretion are not known. We superfused rat antral segments with selective neural agonists/antagonists to identify the neural pathways regulating ANP secretion. The nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) stimulated ANP secretion; the effect was abolished by hexamethonium but doubled by atropine. Atropine's effect implied that DMPP activated concomitantly cholinergic neurons that inhibit and noncholinergic neurons that stimulate ANP secretion, the latter effect predominating. Methacholine inhibited ANP secretion. Neither bombesin nor vasoactive intestinal polypeptide stimulated ANP secretion, whereas pituitary adenylate cyclase-activating polypeptide (PACAP)-27, PACAP-38, and maxadilan [PACAP type 1 (PAC1) agonist] each stimulated ANP secretion. The PAC1 antagonist M65 1) abolished PACAP-27/38-stimulated ANP secretion; 2) inhibited basal ANP secretion by 28 +/- 5%, implying that endogenous PACAP stimulates ANP secretion; and 3) converted the ANP response to DMPP from 109 +/- 21% above to 40 +/- 5% below basal, unmasking the cholinergic component and indicating that DMPP activated PACAP neurons that stimulate ANP secretion. Combined atropine and M65 restored DMPP-stimulated ANP secretion to basal levels. ANP secretion in the antrum is thus regulated by intramural cholinergic and PACAP neurons; cholinergic neurons inhibit and PACAP neurons stimulate ANP secretion.     

PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brain stem. The extent of its localization within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemistry and in situ hybridization, we determined the extent of any colocalization with catecholaminergic and/or bulbospinal projections from the brain stem was determined. PACAP mRNA was found in tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the C1-C3 cell groups. In the rostral ventrolateral medulla (RVLM), PACAP mRNA was found in 84% of the TH-ir neurons and 82% of bulbospinal TH-ir neurons. The functional significance of these PACAP mRNA positive bulbospinal neurons was tested by intrathecal administration of PACAP-38 in anaesthetized rats. Splanchnic sympathetic nerve activity doubled (110%) and heart rate rose significantly (19%), although blood pressure was unaffected. In addition, as previously reported, PACAP was found in the A1 cell group but not in the A5 cell group or in the locus coeruleus. The RVLM is the primary site responsible for the tonic and reflex control of blood pressure through the activity of bulbospinal presympathetic neurons, the majority of which contain TH. The results indicate 1) that pontomedullary neurons containing both TH and PACAP that project to the intermediolateral cell column originate from C1-C3 and not A5, and 2) intrathecal PACAP-38 causes a prolonged, sympathoexcitatory effect.     

Identification and functional properties of the pituitary adenylate cyclase activating peptide (PAC1) receptor in human benign hyperplastic prostate

Pituitary adenylate cyclase activating peptide (PACAP) is a novel neuropeptide with regulatory and trophic functions that is related to vasoactive intestinal peptide (VIP). Here we investigate the expression of specific PACAP receptors (PAC1) and common VIP/PACAP receptors (VPAC1 and VPAC2) in the human hyperplastic prostate by immunological methods. The PAC1 receptor corresponded to a 60-KDa protein whereas the already known VPAC1 and VPAC2 receptors possessed molecular masses of 58 and 68 KDa, respectively. The heterogeneity of VIP/PACAP receptors in this tissue was confirmed by radioligand binding studies using [125I]PACAP-27 by means of stoichiometric and pharmacological experiments. At least two classes of PACAP binding sites showing different affinities could be resolved, with Kd values of 0.81 and 51.4 nM, respectively. The order of potency in displacing [125I]PACAP-27 binding was PACAP-27 approximately equal to PACAP-38 > VIP. PACAP-27 and VIP stimulated similarly adenylate cyclase activity, presumably through common VIP/PACAP receptors. The PAC1 receptor was not coupled to activation of either adenylate cyclase, nitric oxide synthase, or phospholipase C. It appears to be a novel subtype of PAC1 receptor because PACAP-27 (but not PACAP-38 or VIP) led to increased phosphoinositide synthesis, an interesting feature because phosphoinositides are involved via receptor mechanisms in the regulation of cell proliferation.     

Local regulation of anion secretion by pituitary adenylate cyclase-activating polypeptide in human colonic T84 cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel hypothalamic peptide, which has been shown to exert various functions in a number of tissues, including exocrine and endocrine tissues. The present study investigated the role of local PACAP in the control of anion secretion by the human colonic T84 cell. Both bioactive forms of PACAP-27 and PACAP-38 gave rise to a dose-dependent increase in the short-circuit current (I(SC)). However, there was a reversal in the order of potency observed at different concentration ranges for the two bioactive forms. PACAP-27 was greater than PACAP-38 when the peptide concentrations were below 10 n m; PACAP-38 was greater than PACAP-27 in the range of 10-80 n m. The effects of both PACAP forms were restricted to the apical aspect of the T84 cell. The I(SC)responses to both PACAP-27 and PACAP-38 were suppressed respectively by the non-selective Cl(-)channel blocker, diphenylamine-dicarboxylic acid (DPC), by the Ca(2+)dependent Cl(-)channel blocker, diisothiocyanatostilbene-disulfonic acid (DIDS) and by the Ca(2+)chelator, BAPTA-AM, indicating the involvement of Ca(2+). The expression of PACAP was demonstrated and localized specifically to the perinuclear cytoplasm of the T84 cell using immunocytochemistry, indicating its epithelial origin. Thus, the present data suggest that, in addition to the well-known cAMP-dependent pathway, PACAP may play a role in regulating colonic Cl(-)secretion via a Ca(2+)-dependent pathway, perhaps through two distinct PACAP receptor subtypes. Moreover, the regulation of anion secretion by T84 cells may be mediated by locally formed PACAP in an autocrine or paracrine fashion.     

PACAP release from the canine adrenal gland in vivo: its functional role in severe hypotension

This study was to investigate if endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) can be released during direct splanchnic nerve stimulation in vivo and to determine whether PACAP in the adrenal gland can modulate the medullary response to sympathoadrenal reflex. The output of adrenal catecholamine and PACAP-38-like immunoreactivity (PACAP-38-ir) increased in a frequency-dependent manner after direct splanchnic nerve stimulation (0.2-20 Hz). Both responses were highly reproducible, and PACAP-38-ir output closely correlated with catecholamine output. Sodium nitroprusside (SNP; 0.1 mg/kg iv bolus) caused a severe hypotension resulting in marked increases in catecholamine secretion. In the presence of local PACAP-27 (125 ng), the maximum catecholamine response to SNP was significantly potentiated in a synergistic manner compared with that obtained in the group receiving SNP or PACAP-27 alone. The study indicates that endogenous PACAP-38 can be released particularly when the sympathoadrenal system is highly activated and that the local exogenous PACAP-27 enhanced the reflex-induced catecholamine release, suggesting collectively a facilitating role of PACAP as neuromodulator in the sympathoadrenal function in vivo.     

Identification of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type 1 receptor in human skin: expression of PACAP-38 is increased in patients with psoriasis

Morphological and biochemical evidence is presented for the presence of pituitary adenylate cyclase activating peptide (PACAP) and the high-affinity PACAP-1 receptor subtype in human skin. Immunohistochemical analysis revealed PACAP-immunoreactivity (IR) to be present predominantly in dermal nerve fibers close to the dermal-epidermal border, hair follicles, blood vessels and sweat glands. Radioimmunoassay, chromatographic analysis and Western blotting revealed this PACAP-IR to be PACAP-38 whereas the second molecular form, PACAP-27, is absent. In tissue of psoriasis patients significantly more PACAP-38 protein was detected as compared to normal skin. Using RT-PCR, the expression of a high-affinity PACAP-1 receptor in human skin was observed. These results indicate a possible role for PACAP-38 in inflammatory processes of psoriasis.     

Differences in Action of PACAP-27 and PACAP-38 on Guinea Pig Gallbladder Smooth Muscle Using Synthetic C-terminally Modified PACAP Peptides

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two bioactive forms, PACAP-38 and PACAP-27 that have identical N-terminal sequences but differ by the presence of a C-terminal 11 residue elongation in the former. Although VIP and PACAP have several similar biological actions due to their amino acid sequence similarity, we have found that they evoke opposite responses in the guinea pig gallbladder smooth muscle, where PACAP induces contraction while VIP causes relaxation. In addition the response to PACAP-38 is four times lower than that of PACAP-27. In a previous study we have reported the role of the N-terminal α-helical regions of PACAP-27 which play a key role in gallbladder contraction. In the present study the biological action on the guinea pig gallbladder was investigated using a synthetic mini-library of C-terminally deleted peptides related to PACAP-38. The effects caused by residues within the C-terminus are not a result of a response via the M-receptor or Na⁺ channel, but most likely arise from a delicate balance between the differential effects of PACAP-38 on specific PAC1 and VPACs receptors.     

Effect of pituitary adenylate cyclase activating polypeptide on rat pancreatic exocrine secretion.

A novel neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), which has been isolated from ovine hypothalami, shows 68% homology with vasoactive intestinal peptide (VIP). Since VIP stimulates amylase secretion from the pancreas, we investigated the effect of PACAP and VIP on rat pancreatic exocrine secretion after intravenous injections of PACAP-27, PACAP-38, or VIP at doses of 2.5, 5 or 10 nmol/kg. Results showed: 1) Bolus injection of PACAP stimulated pancreatic amylase and protein secretions in a dose-dependent manner; and 2) Stimulation of amylase secretion with 10 nmol/kg of PACAP-27 was greater than that induced with the same dose of VIP or PACAP-38 (p less than 0.05).