UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myotropic effect of pituitary adenylate cyclase-activating polypeptide (PACAP), a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), was studied in the isolated guinea pig ileum in vitro. PACAP contracts the guinea pig ileum significantly more potently and efficiently compared with VIP. PACAP-induced contraction was abolished by tetrodotoxin, dynorphin, and somatostatin, partially reduced by atropine, and not affected by ganglionic and adrenergic blockade. The atropine-resistant component was sensitive to spantide, to the induction of tachyphylaxis with substance P, and to omega-conotoxin. Ileal strips desensitized to PACAP did not respond to VIP, although they maintained their sensitivity to PACAP after desensitization to VIP. COOH-terminal-truncated derivatives of PACAP exhibited full biological activity, although some of them showed substantially reduced potency. Deletion of NH2-terminal amino acids abolished biological activity. PACAP produced a concentration-dependent increase in the release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations preloaded with [3H]choline. This effect was Ca2+ dependent, tetrodotoxin sensitive, and resistant to hexamethonium and scopolamine. In contrast, PACAP inhibited release of acetylcholine evoked by field stimulation. In summary, PACAP-induced contraction of the guinea pig ileum is mediated via release of acetylcholine and substance P through interaction with PACAP-1 and VIP/PACAP-2 receptors. PACAP has to be added to the list of myotropic neuropeptides of the gastrointestinal tract.
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PMID:PACAP is a stimulator of neurogenic contraction in guinea pig ileum. 836 12

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
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PMID:Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. 863 27

Immunohistochemical studies using an antibody against pituitary adenylate cyclase activating polypeptide-38 (PACAP) were performed on spinal cords and dorsal root ganglia harvested from two human cadavers. PACAP-like immunoreactivity (PACAP-LI) was detected in nerve fibers of the superficial layers of the dorsal horn, a few of which extended into the deeper laminae and as far as the ventral horn. At the thoracic segments, additional PACAP-LI nerve fibers were seen in the lateral funiculus projecting into the intermediolateral cell column. Dorsal root ganglia contained numerous PACAP-LI cell bodies of varying intensity. As a control, immunoreactivity to calcitonin gene-related peptide (CGRP) and substance P(SP) was also studied and found to be in nerve fibers of the substantia gelatinosa of the dorsal horn and in dorsal root ganglion cells. These results show that the pattern of distribution of PACAP-LI in the human spinal cord and dorsal root ganglia is similar to that of rodents and further suggest that PACAP may participate in sensory and autonomic functions.
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PMID:Pituitary adenylate cyclase activating polypeptide-immunoreactivity in human spinal cord and dorsal root ganglia. 879 5

The dorsal vagal complex (DVC) and nucleus raphe obscurus (nROb) are currently known to control vagal outflow to the stomach and the pancreas. Elucidation of neurotransmitters in these nuclei that control vagal outflow has become necessary to determine the endogenous circuitry for control of gastric motor activity and pancreatic hormone secretion. In this review, the author's data on the effects of selected peptides on intragastric pressure and gastric contractility as well as on pancreatic glucagon and insulin secretion in the DVC and nROb are presented. Microinjection of thyrotropin-releasing hormone (TRH) or pituitary adenylate cyclase-activating polypeptide (PACAP38) into the nROb results in gastric excitatory motor responses, whereas substance P (SP) and vasoactive intestinal polypeptide (VIP) evoke gastric relaxation. Irrespective of colocalization of TRH and SP in the serotonergic neurons of the nROb, these peptides independently affect gastric motor function when microinjected into the nROb. The inhibitory effect of SP on gastric motor function in the nROb is apparently mediated via nitric oxide in the DVC and involves peripheral VIP, acetylcholine, gamma-aminobutyric acid and nitric oxide. Microinjection of endothelin, PACAP38, and VIP into the DVC evokes increases in gastric motor activity. Pancreatic polypeptide, microinjected into the DVC, does not affect basal plasma insulin and glucagon concentration but potentiates glucose-stimulated insulin secretion. All these data make an important contribution to our understanding of the vagal mechanisms controlling gastric motor and endocrine pancreatic function.
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PMID:Role of selected peptides in the vagal regulation of gastric motor and endocrine pancreatic function. 887 96

The aim of the present study was to evaluate the distribution of pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactivity in the mouse spinal cord using an antibody against PACAP38 and to determine the behavioral profile, particularly with respect to hyperalgesia, of PACAP38 given intrathecally (i.t.) in the mouse. Immunoreactivity to PACAP38 was detected in numerous nerve fibers in the superficial layers of the dorsal horn of cervical, thoracic, lumbar and sacral segments and a few fibers extended into the deeper layers of the spinal cord. In addition, PACAP-like immunoreactivity were seen in the intermediolateral cell column of the thoracic and sacral segments. In behavioral studies, PACAP38 (0.05-0.5 microgram) produced a dose-dependent decrease of the tail-flick latency when given i.t. in the mouse. At higher doses (1-10 micrograms), PACAP38 given i.t. elicited biting and scratching behaviors lasting 10-20 min after the injection. PACAP at high doses (1-10 micrograms) also produced licking at tail, paw and penis and intense grooming behaviors immediately after the i.t. injection. Similar to substance P, these behaviors produced by PACAP can be considered as pain-like syndrome. These findings suggest that PACAP may be a sensory neurotransmitter involved in nociceptive signalling in the mouse spinal cord.
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PMID:Hyperalgesia induced by pituitary adenylate cyclase-activating polypeptide in the mouse spinal cord. 889 91

In vivo and in vitro experiments were undertaken to evaluate the effects of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on rat sympathetic preganglionic neurons (SPNs). Intrathecal injection of PACAP-38 (0.1-1 nmol) via an implanted cannula to the T2-T3 segments of urethane-anesthetized adult rats caused a dose-dependent increase of mean arterial blood pressure from minutes to over 1 h. The pressor response was not antagonized by prior injection of the PACAP type II receptor antagonist PACAP6-38 (0.5 nmol), but was significantly attenuated by prior intravenous administration of phentolamine (1 mg/kg). As a positive control, intrathecal injection of glutamate (1 micromol) and substance P (SP, 5 nmol) caused a short- and long-lasting pressor response. Vasoactive intestinal polypeptide (VIP, 1 nmol) had no significant pressor effect. In the second series of experiments, whole-cell patch recordings were made from antidromically identified SPNs of immature (12-16-day-old) rat thoracolumbar spinal cord slices. Applied to the spinal cord slices by superfusion, PACAP-38 (10-30 nM) caused intense neuronal discharges with or without a long-lasting membrane depolarization. The depolarization was not prevented by superfusing the slices with tetrodotoxin (0.3 microM) or low Ca2+ (0.25 mM) solution, indicating that PACAP-38 directly depolarized the SPNs. The depolarization was insensitive to the type II PACAP receptor antagonist PACAP6-38. Collectively, these results provide evidence that PACAP-38 exerts a potent and long-lasting excitatory effect on SPNs, leading to an increase of spinal sympathetic outflow and one of the consequences of which is an elevation of blood pressure.
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PMID:Excitatory action of pituitary adenylate cyclase activating polypeptide on rat sympathetic preganglionic neurons in vivo and in vitro. 906 61

1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the maximal AFR was 28.1 +/- 2.8 (arbitrary units). 2. ECT also caused release of substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP)-27, -38 and calcitonin gene-related peptide (CGRP). The concentrations of SP and CGRP in the aqueous humour of normal, untreated eyes were 10.6 +/- 1.4 and 117.4 +/- 12.4 pmol l-1, respectively, while the concentrations of PACAP-27 and -38 were below the detection limit. After ECT the concentrations of SP, PACAP-27, -38 and CGRP were 65.0 +/- 9.6, 46.9 +/- 8.4, 50.2 +/- 5.4 and 1109.9 +/- 133.1 pmol l-1, respectively (s.e. of mean, n = 12). Conceivably, ECT evoked an antidromic activation of sensory neurones in the trigeminal ganglion with the consequent release of neuropeptides from C-fibres in the uvea and the development of neurogenic inflammation. 3. Rabbits received the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 200 mg kg 1, i.v.). This pretreatment inhibited the ECT-evoked conjunctival hyperaemia, miosis and AFR: under these circumstances the maximal reduction in pupil size was 1.9 +/- 0.1 mm while the maximal AFR was 2.7 +/- 0.9 (n = 16). L-NAME also inhibited the ECT-evoked release of SP, PACAP-27, -38 and CGRP into the aqueous humour; the concentrations of SP and CGRP were 13.2 +/- 1.5 and 204.8 +/- 33.5 pmol l-1, respectively, while PACAP-27 and -38 were below the detection limit (n = 12). 4. The ECT-evoked miosis was also inhibited by pretreatment with the tachykinin receptor antagonist D-Pal9 spantide 11 (90 nmol, intravitreal injection); under these circumstances the maximal reduction in pupil size was only 0.7 +/- 0.03 mm, indicating an important role for SP in the miotic response. Pretreatment of the eye with capsaicin, which is known to cause functional ablation of C-fibres, inhibited the conjunctival hyperaemia, miosis and AFR by 40-50%; the maximal reduction in pupil size being 2.2 +/- 0.2 mm and the maximal AFR 13.8 +/- 2.1 (arbitrary units) (n = 8). 5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters.
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PMID:Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres. 911 70

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.
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PMID:Immunocytochemical demonstration of pituitary adenylate cyclase activating polypeptide (PACAP) in the porcine epiphyseal cartilage canals. 917 66

The aims of this study were to determine the effect and mechanism of action of pituitary adenylate cyclase-activating peptide (PACAP) on gallbladder muscle. Guinea pig gallbladder muscle strips were studied isometrically. In noncontracted muscle strips, PACAP-27 and PACAP-38 caused dose-dependent contractions, whereas vasoactive intestinal peptide (VIP) caused dose-dependent relaxation. PACAP-27 contractions were resistant to tetrodotoxin, atropine, and the substance P receptor antagonist [D-Arg1,D-Trp7,9,Leu11]substance P (Spantide) but were inhibited by the selective PACAP receptor antagonist PACAP-(6-38) and slightly increased with the VIP receptor antagonist [4-chloro-D-Phe6,Leu17]VIP. In cholecystokinin-precontracted muscle strips, both VIP and PACAP caused relaxations. This relaxant effect of PACAP-27 was inhibited by PACAP-(6-38) and [4-chloro-D-Phe6,Leu17]VIP, but not by tetrodotoxin. These studies suggest that PACAP has dual excitatory and inhibitory effects on guinea pig gallbladder muscle. The contractile effect of PACAP is a direct action on muscle through PACAP-preferring receptors. The relaxant effect of PACAP is seen in precontracted muscle strips and mediated through VIP/ PACAP-preferring receptors.
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PMID:Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/PACAP-preferring receptors. 922 79

Unlike its effects on the rest of the GI tract, the effects of pituitary adenylate cyclase-activating peptide (PACAP) on the internal anal sphincter (IAS) are not known. We examined the actions of PACAP-38 (here PACAP) and PACAP-27 on the basal IAS tone of circular smooth muscle strips before and after the administration of different neurohumoral antagonists. PACAP caused a concentration-dependent fall in the basal tone of the IAS. Interestingly, however, at higher concentrations, PACAP caused a biphasic response: an initial contraction followed by a relaxation. Both the contractile and the relaxant responses were insensitive to atropine, guanethidine, apamin or tetrodotoxin. Both the contractile and the relaxant effects were inhibited by PACAP 6-38 (a selective antagonist of PACAP), vasoactive intestinal polypeptide 10-28 (a vasoactive intestinal polypeptide antagonist) and PACAP tachyphylaxis. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine attenuated the inhibitory but not the excitatory effect of PACAP. Conversely, the contractile but not the relaxant effect of PACAP on the IAS was nearly obliterated by the substance P antagonist spantide. The N-type Ca++-channel blocker omega-conotoxin caused significant suppression of both the contractile and the inhibitory actions of PACAP. We conclude that in the IAS, PACAP has a dual effect: a contraction followed by a relaxation. The contraction of IAS by PACAP is speculated to occur via the activation of PACAP receptor at the substance P-containing nerve terminals. PACAP-induced IAS relaxation, on the other hand, appears to be mediated in large part by its direct action at the smooth muscle cells and in part by its action at the nerve terminals of the myenteric inhibitory neurons.
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PMID:Excitatory and inhibitory actions of pituitary adenylate cyclase-activating peptide (PACAP) in the internal anal sphincter smooth muscle: sites of actions. 935 91

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