UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic and pulmonary vascular responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with 68% sequence homology to vasoactive intestinal peptide (VIP), were investigated in the anesthetized cat. Intravenous injections of PACAP in doses of 0.1-3.0 nmol/kg produced decreases in arterial pressure (AP) at low doses and biphasic changes (decreases followed by increases) at higher doses, which were accompanied by increases in central venous pressure (CVP) and cardiac output (CO), and decreases and biphasic changes in systemic vascular resistance (SVR). In contrast, VIP in doses of 0.1-3.0 nmol/kg produced only dose-dependent decreases in AP and SVR and produced little change in CVP and CO. PACAP produced increased pulmonary arterial pressure (PAP), left atrial pressure (LAP), and increases in pulmonary vascular resistance (PVR). PACAP increased heart rate (HR) and right ventricular contractile force (RVCF), while VIP had no effect. Increases in AP and SVR in response to PACAP were changed to decreases following the administration of phentolamine or after adrenalectomy. Under constant flow conditions, PACAP and VIP produced dose-dependent decreases in lobar arterial pressure when tone was elevated, with PACAP being threefold more potent than VIP. Meclofenamate and nitro-L-arginine methyl ester (L-NAME) had no effect on pulmonary responses to the peptides. PACAP produced dose-dependent biphasic changes in hindquarters perfusion pressure, whereas VIP produced only decreases that were unchanged by indomethacin, L-NAME, and glibenclamide. Phentolamine and adrenalectomy eliminated the hindquarters pressor response to PACAP and D-Phe2-VIP, a VIP antagonist, reduced responses to VIP but not to PACAP. These data suggest that responses to PACAP and VIP are mediated by distinct receptors and that pressor responses to PACAP are due to the release of catecholamines from the adrenal gland.
...
PMID:Analysis of systemic and pulmonary vascular responses to PACAP and VIP: role of adrenal catecholamines. 148 92

Responses to substance P were investigated in the pulmonary vascular bed of the cat with controlled pulmonary blood flow and constant left atrial pressure. Under baseline conditions, intralobar injections of substance P caused small, inconsistent reductions in lobar arterial pressure (AP) and significant reductions in mean systemic AP without affecting left atrial pressure. Decreases in lobar AP were significant and dose related when lobar vascular resistance was increased with U-46619, a thromboxane A2 mimetic. When compared with other vasodilator agents, the order of potency was substance P approximately bradykinin > pituitary adenylate cyclase activating polypeptide (PACAP) > acetylcholine (in nmol). Pulmonary vasodilator responses to substance P were unchanged by administration of atropine, glibenclamide, or sodium meclofenamate or when airflow to the left lower lung lobe was interrupted by bronchial occlusion. The NO synthesis inhibitor, N omega-nitro-L-argininemethyl ester (L-NAME), and the soluble guanylate cyclase inhibitor, methylene blue (MB), selectively inhibited pulmonary vasodilator responses to substance P and to acetylcholine. MB or L-NAME had no significant effect on pulmonary vasodilator responses to albuterol, lemakalim, or PACAP, whereas MB inhibited and L-NAME enhanced vasodilator responses to NO and sodium nitroprusside. The present investigation demonstrates that, when tone is increased experimentally, substance P has potent pulmonary vasodilator activity, and responses are not dependent on changes in bronchomotor tone, on the activation of muscarinic receptors or ATP-sensitive K+ channels, or on the release of a dilator prostaglandin but do involve, at least in part, endothelium-derived NO release and soluble guanylate cyclase activation.
...
PMID:Analysis of responses to substance P in the pulmonary vascular bed of the cat. 768 May 35

1. Regional haemodynamic responses to the homologous peptides, pituitary adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg-1 h-1) in conscious, chronically-instrumented, Long Evans rats. 2. PACAP27 caused dose-dependent depressor and tachycardic effects associated with renal, mesenteric and hindquarters vasodilatations, although only in the latter vascular bed was there a sustained increase in flow. 3. VIP caused dose-dependent depressor and tachycardic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator effects of VIP (at 7.5 and 15 nmol kg-1 h-1) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4. In the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 11 mumol kg-1 h-1), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nmol kg-1 h-1). Under these circumstances the renal and mesenteric vasoconstrictor effects of VIP were abolished. 5. The beta 2-adrenoceptor antagonist, ICI 118551 (670 nmol kg-1 bolus, 335 nmol kg-1 h-1 infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg-1 h-1) and VIP (7.5 nmol kg-1 h-1), and also abolished the renal vasoconstrictor effects of VIP. 6. The AT1-receptor antagonist, losartan potassium (20 mumol kg-1), had no significant effect on the haemodynamic response to PACAP27 (15 nmol kg-1 h-1), but augmented the hypotensive action of VIP (7.5 nmol kg-1 h-1). This influence of losartan was associated with conversion of the renal and mesenteric vasoconstrictor effect of VIP to vasodilatation. 7. Our findings show that similar changes in mean systemic arterial blood pressure in response to PACAP27 and VIP conceal substantial differences in their regional haemodynamic actions. Although the hindquarters vasodilator effects of both peptides involve NO- and Beta2-adrenoceptor-mediated mechanisms,it appears that activation of the renin-angiotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.
...
PMID:Regional haemodynamic responses to pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide in conscious rats. 791 21

1. The actions of nitric oxide (NO) have been investigated in an endotoxin-evoked ocular inflammatory model in the rabbit, with particular emphasis on the relationship between NO, sensory nerves (C-fibres) and the C-fibre neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP). 2. Endotoxin, injected intravitreally, evoked inflammatory responses, i.e. conjunctival hyperaemia, miosis and protein extravasation, reflected by the aqueous flare response (AFR). In control rabbits, the maximum AFR was 66.5 +/- 9.5 (arbitrary units). Pretreatment with the NO synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NAME, 200 mg kg-1) given by intravenous injection, inhibited the endotoxin-evoked responses; the AFR was 16.5 +/- 1.9 (n = 8, P < 0.001) and the conjunctival hyperaemia was abolished. 3. Endotoxin-evoked ocular inflammation is associated with the release of CGRP and PACAP from C-fibres. In the eyes challenged with endotoxin, the concentrations of PACAP-27, -38 and CGRP in the aqueous humour were 58.2 +/- 10.9, 54.4 +/- 12.4 and 5526 +/- 519 (pmoll'), respectively. L-NAME inhibited the release of PACAP-27, -38 and CGRP; the concentrations were 14.3 +/- 2.5, 13.5 +/- 2.5 and 510 +/- 67 (pmoll-1), respectively (n = 8, P < 0.01 or 0.001). 4. Intravitreal injection of 0.3 nmol CGRP induced conjunctival hyperaemia and AFR; the maximum AFR was 140.2 +/- 11.4. L-NAME suppressed the response induced by CGRP; the AFR was 23.4 +/- 5.5 (n = 8, P < 0.001). L-NAME abolished the conjunctival hyperaemia induced by PACAP-27 and -38 (0.3 nmol) and reduced the AFR. 5. The inflammatory cells that infiltrated the uvea, cornea and aqueous humour in large numbers in response to intravitreal injection of endotoxin were found to express inducible NOS. L-NAME prevented the appearance of such cells. 6. Our findings suggest that NO plays an important role in the endotoxin-evoked ocular inflammation in the rabbit: NO activates C-fibres causing release of C-fibre neuropeptides into the aqueous humour. In addition, NO mediates scme of the ocular effects of CGRP and PACAP, since L-NAME suppressed the AFR induced by these peptides.
...
PMID:The contribution of nitric oxide to endotoxin-induced ocular inflammation: interaction with sensory nerve fibres. 883 83

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.
...
PMID:Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres. 911 70

The hemodynamic actions of pituitary adenylate cyclase-activating polypeptide (PACAP-27) rapidly diminish upon repeated i.v. injection in rats treated with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). We now report that the beta-adrenoceptor agonist isoproterenol (0.5 microg/kg, i.v.) produces pronounced hypotensive and vasodilator effects in anesthetized rats pretreated with L-NAME (100 micromol/kg, i.v.). However, the hypotensive and vasodilator actions of isoproterenol were markedly diminished in L-NAME-treated rats in which tachyphylaxis to PACAP was induced immediately prior to the injection of the beta-adrenoceptor agonist. This suggests that a reduction in tissue concentrations of nitric oxide-containing factors allows tachyphylaxis to PACAP-27-mediated vasodilation to occur in vivo and that this process leads to the heterologous desensitization of beta-adrenoceptor-mediated responses.
...
PMID:Heterologous desensitization of beta-adrenoceptor signal transduction in vivo. 920 76

Relaxant responses to pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38 and vasoactive intestinal peptide (VIP) were examined in rat ileal longitudinal muscle. PACAP-27 was much more potent than PACAP-38 and VIP, with PACAP-38 and VIP being equipotent. The relaxation induced by each of the peptides was unaffected by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (10[-4] M), tetrodotoxin (10[-6] M) or atropine (10[-6] M). Pretreatment with apamin (10[-6] M) abolished the relaxations induced by PACAP-27, but not those induced by PACAP-38 or VIP. Pretreatment with neuropeptide Y (NPY) (10[-7] M) inhibited relaxations induced by VIP, but not those induced by PACAP-27 or PACAP-38. No cross-desensitization between PACAP-27 and VIP could be revealed. In conclusion, distinct receptors mediate PACAP- and VIP-induced relaxations of rat ileal longitudinal muscle. At least three different types of receptors may exist: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca2+-dependent K+ channels, (2) a PACAP specific receptor activated by both PACAP-27 and PACAP-38 but not by VIP and (3) a VIP specific receptor regulated by NPY by yet unknown mechanisms.
...
PMID:Distinct receptors mediate pituitary adenylate cyclase-activating peptide- and vasoactive intestinal peptide-induced relaxation of rat ileal longitudinal muscle. 934 29

The pharmacological properties of non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission were investigated in the rabbit choledocho-duodenal junction (CDJ), using the microelectrode and tension recording methods. L-NAME (10(-4) M) and apamin (5 X 10 (-6) M) suppressed NANC relaxation evoked by electrical field stimulation (EFS) in the presence of atropine and guanethidine (each 10(-6) M) to a similar extent (to about 40% of the initial control). However, combined application of L-NAME (10(-4) M) and apamin (5 X 10(-6) M) did not abolish it. EFS also evoked biphasic inhibitory junction potentials (IJPs) consisting of initial fast and slow sustained components in the presence of atropine and guanethidine (each 10(-6) M). Apamin (5 X 10(-8)-5 X 10(-6) M) dose-dependently suppressed the initial fast component by about 70%. In contrast, L-NAME (10(-4) M) did not affect either the amplitude of IJP or the resting membrane potential. PACAP-38 (> 10(-8) M) dose-dependently hyperpolarized the smooth muscle membrane of rabbit CDJ followed by a slow repolarization to the original level. After pretreatment with apamin (5 X 10(-7) M), PACAP-38 (10(-6) M) failed to evoke membrane hyperpolarization. During repolarization in the continued presence of PACAP-38, the amplitude of initial fast component of IJP was reduced to about 40-60% of control value, while that of the slow one was unaffected. A similar suppression of initial fast component of IJP (about 40% of the control value) also occurred after application of PACAP (6-38), a PACAP antagonist, or prolonged treatment with monoclonal antibodies to PACAP-27 or PACAP-38. Furthermore, the substantial part of residual fast IJP in the presence of PACAP (6-38) was suppressed by desensitization to alpha,beta-methylene ATP (10(-3) M). These results indicate that in rabbit CDJ NANC relaxation consists mainly of apamin- and L-NAME-sensitive components, which occur in a membrane potential dependent (through membrane hyperpolarization) and independent fashion, respectively. It has further been suggested that PACAP, together with a smaller contribution of ATP, may be involved as the principal apamin-sensitive transmitter in NANC relaxation of this muscle.
...
PMID:Inhibitory NANC neurotransmission in choledocho-duodenal junction of rabbits--a possible role of PACAP. 970 61

To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
...
PMID:The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit. 972 56

The aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthetized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the expression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 produced dose-dependent decreases in mean arterial blood pressure and hindquarter and mesenteric vascular resistances in saline-treated rats. PACAP-27 also produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensive and vasodilator actions of PACAP-27 were not attenuated by the beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME 50 micromol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 microg/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of adrenal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produces tachycardia by directly releasing norepinephrine from cardiac sympathetic nerve terminals rather than by direct or baroreceptor reflex-mediated increases in sympathetic nerve activity.
...
PMID:Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat. 998 4

1 2 Next >>