Actions of calcitonin gene-related peptide in guinea pig gallbladder ganglia

1996 ◽  
Vol 271 (5) ◽  
pp. G876-G883 ◽  
Author(s):  
A. P. Gokin ◽  
L. J. Jennings ◽  
G. M. Mawe

The actions of calcitonin gene-related peptide (CGRP) have been determined from intracellular recordings obtained from gallbladder neurons in intact whole mount preparations. In most cells, pressure microejection of CGRP elicited a slow, monophasic depolarization, 4 mV in amplitude, that was associated with a decrease in input resistance and increased excitability. The CGRP-induced depolarization was attenuated in a low-Na+ solution and had a reversal potential of -8 mV. In 10% of the cells, microejection of CGRP elicited a biphasic response that was composed of a rapid transient depolarization followed by a slow depolarization that was similar to the monophasic response. Addition of CGRP (1–10 nM) to the bathing solution elicited a monophasic depolarization and desensitized the cells to applications of CGRP by microejection. Forskolin, applied either by microejection or bath application, also depolarized gallbladder neurons and produced cross-desensitization to CGRP. Responses to substance P were not enhanced by CGRP, and CGRP did not affect fast synaptic responses. It is concluded that CGRP may contribute to a local axon reflex response in gallbladder ganglia.

2020 ◽  
Author(s):  
Yinlu Liu ◽  
Qi-Yu Chen ◽  
Jung Hyun Lee ◽  
Xu-Hui Li ◽  
Shengyuan Yu ◽  
...  

Abstract Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.


1994 ◽  
Vol 267 (5) ◽  
pp. R1421-R1429 ◽  
Author(s):  
A. M. Reynier-Rebuffel ◽  
P. Mathiau ◽  
J. Callebert ◽  
V. Dimitriadou ◽  
N. Farjaudon ◽  
...  

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.


2013 ◽  
Vol 31 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Hisashi Shinbara ◽  
Masamichi Okubo ◽  
Keisaku Kimura ◽  
Kunio Mizunuma ◽  
Eiji Sumiya

Objective The purpose of this study was to determine how calcitonin gene related peptide (CGRP) via axon reflex participates in increasing local muscle blood flow (MBF) following manual acupuncture (MA). Methods Male Sprague–Dawley rats (N=56, 270–350 g) were used. We examined (1) the effects of MA on MBF in the tibialis anterior (TA) muscle in normal rats; (2) the effects of MA on MBF in the TA injected with saline or hCGRP8-37 (low: 2×10−4 mol/litre; high: 2×10−3 mol/litre), a competitive CGRP receptor antagonist, in rats; and (3) the effects of MA on MBF in the TA in capsaicin-treated rats. The capsaicin-treated rats were injected with capsaicin dissolved in an ethanol solution within 24 h after birth (50 mg/kg subcutaneously). MA was applied to the right TA for 1 min. 51Cr-labelled microspheres (15 μm in diameter) were used to measure MBF. Results MA significantly increased MBF without changing arterial blood pressure in normal rats (p<0.05). MA also significantly increased MBF in saline-injected, low hCGRP8-37-injected and high hCGRP8-37-injected rats (p<0.001, 005 and 0.05, respectively). The increases in low and high hCGRP8-37-injected rats were lower than those in saline-injected rats, but the difference was not significant. However, MA did not significantly increase MBF in capsaicin-treated rats (p=0.38). Conclusions We obtained conflicting results, suggesting that the participation of CGRP released via axon reflex may be limited to a local increase in MBF following MA.


Nature ◽  
1993 ◽  
Vol 363 (6424) ◽  
pp. 76-79 ◽  
Author(s):  
Bai Lu ◽  
Wen-mei Fu ◽  
Paul Greengard ◽  
Mu-ming Poo

1992 ◽  
Vol 133 (2) ◽  
pp. 259-NP ◽  
Author(s):  
A. Y. H. Leung ◽  
P. Y. Leung ◽  
S. B. Cheng-Chew ◽  
P. Y. D. Wong

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


2020 ◽  
Author(s):  
Yinlu Liu ◽  
Qi-Yu Chen ◽  
Jung Hyun Lee ◽  
Xu-Hui Li ◽  
Shengyuan Yu ◽  
...  

Abstract Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.


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