Regional haemodynamic responses to pituitary adenylate cyclase‐activating polypeptide and vasoactive intestinal polypeptide in conscious rats

Gardiner, Sheila M.; Rakhit, T.; Kemp, P.A.; March, J E; Bennett, T.

doi:10.1111/j.1476-5381.1994.tb14778.x

Cited by 29 publications

(13 citation statements)

References 26 publications

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“…When rats were given an intravenous injection of 1 nmol/kg of the VPAC1-selective agonist [K15, R16, L27]VIP(1-7)/ GRF (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), it increased plasma insulin levels by twofold, but, consistent with the role of VPAC1 in enhancing hepatic glucose production, it also increased blood glucose levels by 14% 30 min after an IPGTT (data not shown). The VPAC1-selective agonist displayed dosedependent effects on intestinal water retention that were identical to those of VIP, whereas the effect of the VPAC2-selective agonist was much less.…”

Section: Vpac2 Agonist For Type 2 Diabetesmentioning

confidence: 71%

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A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

et al. 2002

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Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) activate two shared receptors, VPAC1 and VPAC2. Activation of VPAC1 has been implicated in elevating glucose output, whereas activation of VPAC2 may be involved in insulin secretion. A hypothesis that a VPAC2-selective agonist would enhance glucose disposal by stimulating insulin secretion without causing increased hepatic glucose production was tested using a novel selective agonist of VPAC2. This agonist, BAY 55-9837, was generated through site-directed mutagenesis based on sequence alignments of PACAP, VIP, and related analogs. The peptide bound to VPAC2 with a dissociation constant (K d ) of 0.65 nmol/l and displayed >100-fold selectivity over VPAC1. BAY 55-9837 stimulated glucose-dependent insulin secretion in isolated rat and human pancreatic islets, increased insulin synthesis in purified rat islets, and caused a dose-dependent increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory concentration of 3 pmol/kg. Continuous intravenous or subcutaneous infusion of the peptide reduced the glucose area under the curve following an intraperitoneal glucose tolerance test. The peptide had effects on intestinal water retention and mean arterial blood pressure in rats, but only at much higher doses. BAY 55-9837 may be a useful therapy for the treatment of type 2 diabetes.

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Section: Vpac2 Agonist For Type 2 Diabetesmentioning

confidence: 71%

“…Cardiovascular effects of BAY 55-9837. Because PACAP27 causes peripheral vasodilation that elicits a compensatory increase in heart rate (14,26,27), the effects of BAY 55-9837 on MAP were determined in rats (Fig. 7).…”

Section: Vpac2 Agonist For Type 2 Diabetesmentioning

confidence: 99%

A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

et al. 2002

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“…PACAP resulted in reduction of free lambda light chains in the urine [26]. It is also known that PACAP increases blood flow of the kidneys and stimulates renin secretion through the activation of pac1 receptor [11,13].…”

mentioning

confidence: 97%

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

László¹,

Kiss²,

Horváth³

et al. 2014

Acta Biologica Hungarica

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pituitary adenylate cyclase activating polypeptide (pacap) is a multifunctional neuropeptide occurring in the nervous system as well as in the peripheral organs. Beneficial action of PACAP has been shown in different pathological processes. The strong protective effects of the peptide are probably due to its complex modulatory actions in antiapoptotic, anti-inflammatory and antioxidant pathways. In the kidney, PACAP is protective in models of diabetic nephropathy, myeloma kidney injury, cisplatin-, gentamycinand cyclosporin-induced damages. Numerous studies have been published describing the protective effect of this peptide in renal ischemia/reperfusion. the present review focuses on the ischemia/reperfusioninduced kidney injury and gives a brief summary about the results published in this area.

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“…Therefore, PACAP induces vasodilation in several vessel types and vascular beds such as coronary, cerebral, and pulmonary arteries; arteries of the skin; hindquarters; and the uteroplacental circulation (4 -10). Moreover, PACAP increases renal blood flow in conscious rats (11) and bears protective effects on myeloma injury of proximal tubular cells (12), providing functional links between PACAP and the kidney. A possible role of PACAP in kidney function has also been suggested by the detection of PACAP-binding sites and PACAP receptor gene expression in the kidney (12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Pituitary Adenylate Cyclase–Activating Polypeptide Stimulates Renin Secretion via Activation of PAC1 Receptors

Hautmann¹,

Friis²,

Desch³

et al. 2007

Journal of the American Society of Nephrology

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Besides of its functional role in the nervous system, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of cardiovascular function. Therefore, PACAP is a potent vasodilator in several vascular beds, including the renal vasculature. Because the kidney expresses both PACAP and PACAP-binding sites, it was speculated that PACAP might regulate cardiovascular function by direct vascular effects and indirectly by regulating renin release from the kidneys. PACAP (1-27) stimulated renin secretion from isolated perfused kidneys of rats 4.9-fold with a half-maximum concentration of 1.9 nmol/L. In addition, PACAP stimulated renin release and enhanced membrane capacitance of isolated juxtaglomerular cells, indicating a direct stimulation of exocytotic events. The effect of PACAP on renin release was mediated by the specific PACAP receptors (PAC1), because PACAP (1-27) applied in concentrations in the physiologic range (10 and 100 pmol/L) did not enhance renin release from isolated kidneys of PAC1 receptor knockout mice (PAC1؊/؊), whereas it stimulated renin release 1.38-and 2.5-fold in kidneys from wild-type mice. Moreover, plasma renin concentration was significantly lower in PAC1؊/؊ compared with their wild-type littermates under control conditions as well as under a lowor high-salt diet and under treatment with the angiotensin-converting enzyme inhibitor ramipril, whereas no differences in plasma renin concentration between the genotypes were detectable after water deprivation. These data show that PACAP acting on PAC1 receptors potently stimulates renin release, serving as a tonic enhancer of the renin system in vivo.

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Regional haemodynamic responses to pituitary adenylate cyclase‐activating polypeptide and vasoactive intestinal polypeptide in conscious rats

Cited by 29 publications

References 26 publications

A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

Pituitary Adenylate Cyclase–Activating Polypeptide Stimulates Renin Secretion via Activation of PAC1 Receptors

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