scholarly journals Effects of Adrenomedullin, Calcitonin Gene-Related Peptide, and Amylin on Cerebral Circulation in Dogs

1995 ◽  
Vol 15 (5) ◽  
pp. 827-834 ◽  
Author(s):  
Mustafa K. Baskaya ◽  
Yoshio Suzuki ◽  
Masaoki Anzai ◽  
Yukio Seki ◽  
Kiyoshi Saito ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Circulation ◽  
Cerebral Arteries ◽  
Calcitonin Gene Related Peptide ◽  
Bolus Administration ◽  
Dependent Manner ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

The effect of human adrenomedullin on cerebral circulation was investigated in dogs in vivo and in vitro. Bolus administration of adrenomedullin or its homologous peptides, calcitonin gene-related peptide (CGRP) and amylin, into the vertebral artery induced a dose-dependent increase in vertebral blood flow. The potencies of adrenomedullin and CGRP were similar and approximately 100 times more than that of amylin. The effects of adrenomedullin and CGRP were inhibited by CGRP8-37, an antagonist of CGRP. In contrast to substance P, adrenomedullin did not induce an increase in blood flow after prior administration of CGRP. Pretreatment with either NG-nitro-l-arginine methyl ester or indomethacin did not affect the adrenomedullin-induced increase in blood flow. Intracisternal administration of adrenomedullin induced dilation of the basilar and other major cerebral arteries in a dose-dependent manner, accompanied by an increase in the concentration of cyclic AMP in the cerebrospinal fluid. Adrenomedullin also induced relaxation of isolated basilar and middle cerebral arterial rings. These data suggest that adrenomedullin induces vasodilation of cerebral arteries and an increase in vertebral blood by acting at CGRP receptors positively coupled to adenylate cyclase, and that these effects are not dependent on nitric oxide or prostaglandin formation.

scholarly journals Renal microvascular actions of calcitonin gene-related peptide

1998 ◽  
Vol 274 (6) ◽  
pp. F1078-F1085 ◽  
Author(s):  
Martina Reslerova ◽  
Rodger Loutzenhiser
Keyword(s):  
Angiotensin Ii ◽  
Rat Kidney ◽  
Elevated Pressure ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Renal Vasoconstriction ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 ± 10% inhibition). These effects were partially attenuated by 10 μM glibenclamide (62 ± 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 ± 11%, and this action was not affected by glibenclamide (41 ± 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 μM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 ± 5 and 59 ± 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.

Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium

1986 ◽  
Vol 250 (4) ◽  
pp. H693-H698 ◽  
Author(s):  
A. Saito ◽  
S. Kimura ◽  
K. Goto
Keyword(s):  
Guinea Pig ◽  
Right Atrium ◽  
Sinus Node ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Chronotropic Response ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Right

The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.

Calcitonin gene-related peptide promotes angiogenesis via AMP-activated protein kinase

2010 ◽  
Vol 299 (6) ◽  
pp. C1485-C1492 ◽  
Author(s):  
Shuai Zheng ◽  
Wenjing Li ◽  
Mingjiang Xu ◽  
Xue Bai ◽  
Zhou Zhou ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Calcitonin Gene Related Peptide ◽  
Tube Formation ◽  
Dependent Manner ◽  
Related Peptide ◽  
Compound C ◽  
Calcitonin Gene ◽  
And Migration ◽  
Amp Activated Protein Kinase

Ischemia induces angiogenesis as a compensatory response. Although ischemia is known to causes synthesis and release of calcitonin gene-related peptide (CGRP), it is not clear whether CGRP regulates angiogenesis under ischemia and how does it function. Thus we investigated the role of CGRP in angiogenesis and the involved mechanisms. We found that CGRP level was increased in the rat hindlimb ischemic tissue. The expression of exogenous CGRP by adenovirus vectors enhanced blood flow recovery and increased capillary density in ischemic hindlimbs. In vitro, CGRP promoted human umbilical vein endothelial cell (HUVEC) tube formation and migration. Further more, CGRP activated AMP-activated protein kinase (AMPK) both in vivo and in vitro, and pharmacological inhibition of CGRP and cAMP attenuated the CGRP-activated AMPK in vitro. CGRP also induced endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs at Ser1177 and Ser633 in a time-dependent manner, and such effects were abolished by AMPK inhibitor Compound C. As well, Compound C blocked CGRP-enhanced HUVEC tube formation and migration. These findings indicate that CGRP promotes angiogenesis by activating the AMPK-eNOS pathway in endothelial cells.

Interaction of Calcitonin Gene-Related Peptide, Nitric Oxide and Histamine Release in Neurogenic Blood Flow and Afferent Activation in The Rat Cranial Dura Mater

Cephalalgia ◽  
2007 ◽  
Vol 27 (6) ◽  
pp. 481-491 ◽  
Author(s):  
N Schwenger ◽  
M Dux ◽  
R de Col ◽  
R Carr ◽  
K Messlinger
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Histamine Release ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Blockade ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), nitric oxide (NO) and histamine are implicated in primary headaches but their role in vascular and nociceptive events in the dura mater is not well described. In an in vitro preparation of the hemisected rat skull, CGRP and histamine release from the cranial dura was measured using enzyme-linked immunoassays. While the NO donator NONOate (10-4 M) was without effect, CGRP (10-5 M) induced considerable histamine release from the rat cranial dura, which was blocked by the CGRP receptor antagonist CGRP8-37 (10-5 M). Conversely, histamine (10-4 M) did not stimulate CGRP release. In vitro recordings from single rat meningeal afferents showed that only one of 12 mechanically identified units but several mechanically insensitive units responded to histamine (up to 10-5 M). Increases in meningeal blood flow after histamine application (10-4 M) to the rat cranial dura remained unchanged during CGRP receptor blockade with CGRP8-37, inhibition of NO synthesis with L-NAME (20 mg/kg i.v.) and H3 receptor blockade with thioperamide (10-4 M). We conclude that histamine produces direct vasodilatation and activates a subset of largely non-mechanically sensitive, non-CGRP containing afferents in the rat meninges. Histamine is released from meningeal mast cells which are stimulated by CGRP. Similar mechanisms may be involved in the pathogenesis of headaches.

Calcitonin gene related peptide relaxes cholecystokinin-induced contraction in guinea pig gallbladder strips in vitro

1992 ◽  
Vol 70 (12) ◽  
pp. 1571-1575 ◽  
Author(s):  
L. W. Kline ◽  
P. K. T. Pang
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Calcitonin Gene Related Peptide ◽  
Intestinal Smooth Muscle ◽  
Human Calcitonin ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide8–37. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG-nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin-induced contraction observed in the guinea pig gallbladder strips.Key words: calcitonin gene related peptide, gallbladder, cholecystokinin.

Gene transfer of calcitonin gene-related peptide to cerebral arteries

2000 ◽  
Vol 278 (2) ◽  
pp. H586-H594 ◽  
Author(s):  
Kazunori Toyoda ◽  
Frank M. Faraci ◽  
Andrew F. Russo ◽  
Beverly L. Davidson ◽  
Donald D. Heistad
Keyword(s):  
Cerebrospinal Fluid ◽  
Gene Transfer ◽  
Basilar Artery ◽  
Cultured Cells ◽  
Cerebral Arteries ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

Overexpression of calcitonin gene-related peptide (CGRP), an extremely potent vasodilator, to blood vessels is a possible strategy for prevention of vasospasm. We constructed an adenoviral vector that encodes prepro-CGRP (Adprepro-CGRP) and examined the effects of gene transfer on cultured cells and cerebral arteries. Transfection of Adprepro-CGRP to Cos-7 and NIH-3T3 cells increased CGRP-like immunoreactivity in media and produced an increase in cAMP in recipient cells. Five days after injection of Adprepro-CGRP into the cisterna magna of rabbits, the concentration of CGRP-like immunoreactivity increased by 93-fold in cerebrospinal fluid. In basilar artery, cAMP increased by 2.3-fold after Adprepro-CGRP compared with a control adenovirus. After transfection of Adprepro-CGRP, contraction of basilar artery in vitro to histamine and serotonin was attenuated, and relaxation to an inhibitor of cyclic nucleotide phosphodiesterase 3-isobutyl-1-methylxanthine was augmented compared with nontransduced arteries or arteries transfected with a control gene. Altered vascular responses were restored to normal by pretreatment with a CGRP1 receptor antagonist CGRP-(8–37). Thus gene transfer of prepro-CGRP in vivo overexpresses CGRP in cerebrospinal fluid and perivascular tissues and modulates vascular tone. We speculate that this approach may be useful in prevention of vasospasm after subarachnoid hemorrhage.

Characteristics of relaxation induced by calcitonin gene—related peptide in contracted rabbit basilar artery

1995 ◽  
Vol 82 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Bernhard Sutter ◽  
Satoshi Suzuki ◽  
Neal F. Kassell ◽  
Kevin S. Lee
Keyword(s):  
Basilar Artery ◽  
Contractile Response ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Vascular Response ◽  
Content Type ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent ◽  
Fine Print

✓ Increasing evidence suggests that disturbances in the modulatory influence of the vasoactive peptide, calcitonin gene—related peptide (CGRP), contribute to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, only limited success has been achieved in trials attempting to ameliorate vasospasm by modifying CGRP function. To better understand the potential utility of targeting CGRP-mediated relaxation, it is important both to identify the interactions CGRP may have with other elements of the vasospastic response and to characterize the mechanisms through which CGRP elicits vasodilative effects. The present studies examined the effects of CGRP on vascular responsiveness using tension measurements of ring strips of rabbit basilar artery maintained in vitro. Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to the potent protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDB). This particular contractile response was selected because PKC-mediated vasoconstriction is a critical component of the vasospastic response after SAH. In a posttreatment paradigm, CGRP was also found to reverse established constriction responses to PDB (2 nM) and histamine (3 µM) in a dose-dependent manner. When tested against the maximum effective dose of PDB (30 nM) in the posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation. However, after washing both of these drugs out of the test chamber, a persistent effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated in vessels that had previously been treated with CGRP. These findings indicate that CGRP elicits both immediate and sustained influences on contractile responses mediated by PKC. Finally, two potential mechanisms for the vascular response to CGRP were examined. Adenosine triphosphate (ATP)—sensitive K+ channels do not appear to participate in CGRP-mediated dilation; inhibitors of these channels, glibenclamide and tolbutamide, did not block CGRP-induced relaxation. In contrast, a possible role for the nucleotide cyclic adenosine monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose-dependent elevation of cAMP levels by CGRP. Together these studies indicate that CGRP can modulate the contractile response to PKC activation. These effects are associated with increases in the levels of cAMP, but occur independently of fluxes through ATP-sensitive K+ channels.

The role of calcitonin gene-related peptide in the regulation of anion secretion by the rat and human epididymis

1992 ◽  
Vol 133 (2) ◽  
pp. 259-NP ◽  
Author(s):  
A. Y. H. Leung ◽  
P. Y. Leung ◽  
S. B. Cheng-Chew ◽  
P. Y. D. Wong
Keyword(s):  
Short Circuit ◽  
Calcitonin Gene Related Peptide ◽  
Bathing Solution ◽  
Dependent Manner ◽  
Anion Secretion ◽  
Human Epididymis ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

ABSTRACT A study was carried out to investigate the role of the calcitonin gene-related peptide (CGRP) in the regulation of electrolyte transport in the rat and human epididymis. In monolayer cultures derived from the rat cauda epididymal cells, CGRP stimulated the short-circuit current (SCC) in a dose-dependent manner with the EC50 (concentration required to produce 50% of the response) at 15 nmol/l. This effect of CGRP was seen when the peptide was added to the basolateral aspect of the cells; apical addition having negligible effect. The CGRP-induced rise in the SCC was dependent on the presence of chloride in the bathing solution. Calcitonin had no effect on the SCC and did not affect the CGRP-induced rise in the SCC. The effect of CGRP on secretion was inhibited in a competitive fashion by the CGRP receptor antagonist CGRP(8–37). In contrast to bradykinin, angiotensin II and endothelin I, the effect of CGRP was independent of prostaglandin synthesis. Measurement of intracellular adenosine 3′:5′-cyclic monophosphate showed a time- and dose-dependent increase upon stimulation with CGRP. CGRP also stimulated the SCC in monolayers grown from the human epididymis. The current could be inhibited by apical application of the chloride channel blocker, diphenylamine-2-carboxylate. Immunoreactive CGRP was found in the epithelia of rat and human cauda epididymidis. It is suggested that CGRP may regulate the electrolyte and fluid secretion in the epididymis, thereby providing an optimal microenvironment for the maturation and storage of spermatozoa. Journal of Endocrinology (1992) 133, 259–268

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