Corticotropin-releasing hormone (CRH) receptors in the mesenteric small arteries of rats resemble the (2)-subtype

Rohde, E; Furkert, Jens; Fechner, Klaus; Beyermann, Michael; Mulvany, Michael J.; Richter, R; Denef, Carl; Bienert, Michael; Berger, H.

doi:10.1016/0006-2952(96)00300-0

Cited by 38 publications

(34 citation statements)

References 18 publications

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“…Previous studies of other smooth muscle tissues have shown the same. Although the expression of CRH-selective receptors has been proven in myometrial [21], colonic [29] and arterial [30] smooth muscles, CRH manifested its activity in these tissues only after some excitable stimulus had been applied. Under such conditions, the observed action of CRH was always to inhibit the contractile activity.…”

Section: Discussionmentioning

confidence: 98%

“…CRH is implicated physiologically in the regulation of gastric emptying [26] and in stress-related alterations of gastrointestinal functions [9]. Recent studies indicate that CRH may act as a neuromediator at the peripheral presynaptic nerve terminals to modulate the release of conventional neurotransmitters [27,28], and that various types of smooth muscle possess selective CRH receptors, coupled to an adenylyl cyclase transduction pathway [25,29,30]. All these tissues are potential targets for drugs expressing CRH-like or antagonist activity and their functions may be affected by such drugs during various therapeutic approaches.…”

Section: Contraction Studiesmentioning

confidence: 99%

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Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A

Duridanova

Petkova-Kirova

Lubomirov

et al. 1999

Pfl�gers Archiv European Journal of Physiology

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In contraction studies corticotropin-releasing hormone (CRH) was found to relax ileal but not gastric and jejunal smooth muscles of the guinea-pig, precontracted with BaCl2. Under whole-cell patch-clamp conditions, CRH concentration-dependently activated Ca2+-sensitive K+ currents (IK) with ED50=20 pM at 100 nM and ED50=0. 13 pM at 500 nM intracellular Ca2+ respectively. This increase was accompanied by significant hyperpolarization of the cell membranes. CRH 9-41 peptide fragment did not affect IK amplitude, membrane potential or contraction. The CRH-induced increase of IK densities was accelerated in the presence of high intracellular Ca2+ concentrations (500 nM) and was abolished by pretreatment of cells with either ryanodine or thapsigargin, which cause depletion of intracellular Ca2+ stores, as well as in cells treated under conditions prohibiting intracellular Ca2+ store refilling. The effect of CRH on IK was not affected by bath application of various selective inhibitors of membrane-bound phospholipases, protein kinase C, cGMP-dependent protein kinase or Ca2+/calmodulin-dependent protein kinase II, but was effectively antagonized by blockers of protein kinase A (PKA) or adenylyl cyclase. Neither forskolin nor the catalytic subunit of PKA could mimic the effect of CRH on IK. Thus, it was suggested that CRH exerts its relaxing activity on ileal smooth muscle cells via PKA-dependent phosphorylation of some intracellular target coupled to sarcoplasmic reticulum Ca2+ storage machinery.

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Section: Discussionmentioning

confidence: 98%

Section: Contraction Studiesmentioning

confidence: 99%

Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A

Duridanova

Petkova-Kirova

Lubomirov

et al. 1999

Pfl�gers Archiv European Journal of Physiology

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“…There is clear agreement in the literature that CRF ligands cause mesenteric (Rohde et al, 1996;Barker and Corder, 1999) and coronary (Grunt et al, 1993;Terui et al, 2001;Huang et al, 2002) vasodilatation, but there is no consensus with regard to the mediators involved in those responses or the degree of their dependence on the endothelium. For example, Grunt et al (1993) provided evidence in the isolated rat heart to suggest that the coronary vasodilator action of CRF involved the endothelial release of NO and prostacyclin.…”

Section: Discussionmentioning

confidence: 99%

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

Gardiner

March²,

Kemp³

et al. 2004

J Pharmacol Exp Ther

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In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF 2 ) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg Ϫ1 hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg Ϫ1 , all three peptides caused dosedependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF 2 receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin-and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF 2 receptors and do not involve NO or prostanoids.

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“…In order to investigate whether the length of the connector unit (22)(23)(24)(25)(26)(27)(28)(29)(30)(31) in UEK plays a specific role with respect to biopotency, we synthesized the corresponding deletion analogues.…”

Section: 35mentioning

confidence: 99%

A Role for a Helical Connector between Two Receptor Binding Sites of a Long-chain Peptide Hormone

Beyermann

Rothemund

Heinrich

et al. 2000

Journal of Biological Chemistry

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The conformational freedom of single-chain peptide hormones, such as the 41-amino acid hormone corticotropin releasing factor (CRF), is a major obstacle to the determination of their biologically relevant conformation, and thus hampers insights into the mechanism of ligand-receptor interaction. Since N-and C-terminal truncations of CRF lead to loss of biological activity, it has been thought that almost the entire peptide is essential for receptor activation. Here we show the existence of two segregated receptor binding sites at the N and C termini of CRF, connection of which is essential for receptor binding and activation. Connection of the two binding sites by highly flexible ⑀-aminocaproic acid residues resulted in CRF analogues that remained full, although weak agonists (EC 50 : 100 -300 nM) independent of linker length. Connection of the two sites by an appropriate helical peptide led to a very potent analogue, which adopted, in contrast to CRF itself, a stable, monomer conformation in aqueous solution. Analogues in which the two sites were connected by helical linkers of different lengths were potent agonists; their significantly different biopotencies (EC 50 : 0.6 -50 nM), however, suggest the relative orientation between the two binding sites rather than the maintenance of a distinct distance between them to be essential for a high potency.

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Corticotropin-releasing hormone (CRH) receptors in the mesenteric small arteries of rats resemble the (2)-subtype

Cited by 38 publications

References 18 publications

Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A

Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

A Role for a Helical Connector between Two Receptor Binding Sites of a Long-chain Peptide Hormone

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