Carbamylcholine‐ and 5‐hydroxytryptamine‐induced contraction in rat isolated airways: inhibition by calcitonin gene‐related peptide
21
Citation
34
Reference
10
Related Paper
Citation Trend
Abstract:
The effects of rat and human α‐calcitonin gene‐related peptide (α‐CGRP) were investigated in isolated smooth muscle preparations obtained from three levels of the rat respiratory tract. Neither peptide (10 −10 –10 −6 m ) had any effect on resting tension or on carbamylcholine (10 −6 m )‐induced tone of trachea or main bronchus. In contrast, CGRP sometimes reduced spontaneous or carbamylcholine‐induced tone of lung parenchymal strips. CGRP produced a significant rightward shift of the log concentration‐response curves to carbamylcholine and 5‐hydroxytryptamine (5‐HT) in the main bronchus. A rightward shift was also seen in trachea and parenchymal strips but this did not achieve the level of significance. The maximal response to 5‐HT was reduced in the main bronchus and lung parenchyma whereas the maximal contraction to carbamylcholine was decreased in parenchymal strip only. In all three airway preparations, CGRP caused concentration‐dependent inhibition of responses elicited by challenges with 10 −7 m carbamylcholine or 5 × 10 −7 m 5‐HT. The inhibitory effect of the peptide was inversely related to the size of the airways: the smaller the calibre, the greater the inhibition. The inhibitory action of CGRP was not modified by pretreatment with tetrodotoxin (10 −6 m ), propranolol (10 −6 m ) or indomethacin (10 −6 m ). The results strongly suggest that (a) CGRP has a nonspecific inhibitory action on airway smooth muscle cells, (b) CGRP may act as a potent inhibitor of responses elicited by bronchoconstrictor substances and (c) its inhibitory activity may be most powerfully expressed in peripheral regions of the respiratory tract.Keywords:
Parenchyma
Tetrodotoxin
Cite
Citations (4)
Calcitonin receptor
Cite
Citations (14)
Repetitive stimulation of mammalian fast-twitch skeletal muscles will normally result in a positive staircase response. This phenomenon was investigated in the rat gastrocnemius muscle following a 2-week period of tetrodotoxin-induced disuse. Muscle inactivity was imposed by superfusing tetrodotoxin in saline over the left sciatic nerve via an implanted osmotic pump. In situ isometric contractile responses to double pulse stimulation and repetitive stimulation at 10 Hz were determined the day after removal of the pump. Two weeks of disuse resulted in 40% muscle weight loss. A twitch contraction gave the same force when expressed per gram of wet muscle weight in control muscles, 317 ± 24.6 [Formula: see text] g/g, as compared with tetrodotoxin-treated muscles, 328 ± 24.2 g/g. Both contraction time and half-relaxation time were prolonged following treatment with tetrodotoxin. Repetitive stimulation at 10 Hz resulted in a positive staircase response in the control muscles, but not in muscles of the tetrodotoxin-treated rats. The observed changes in the time course of the twitch contraction with repetitive stimulation following tetrodotoxin-induced disuse are consistent with alterations in sarcoplasmic reticulum handling of calcium. It is not certain if there is a change following disuse in the mechanism normally associated with staircase or if this mechanism is merely opposed by an early fatigue.
Tetrodotoxin
Gastrocnemius muscle
Cite
Citations (14)
Medullary carcinoma
Cite
Citations (1)
Cite
Citations (9)
The mechanisms involved in the long-lasting contraction induced by transmural stimulation were investigated in the isolated longitudinal muscle of the guinea-pig gastric corpus. Transmural stimulation induced an initial rapid contraction, a subsequent relaxation and a long-lasting contraction which was mimicked closely by the responses to noradrenaline and ATP. The rapid contraction was blocked by tetrodotoxin or by atropine, and the subsequent relaxation was also blocked by tetrodotoxin, but not by atropine. The long-lasting contractions were not inhibited by atropine, phentolamine, and propranolol. However, some of those were partially inhibited by tetrodotoxin and guanethidine, and others were enhanced by tetrodotoxin. The noradrenaline- but not ATP-induced long-lasting contraction was blocked by phentolamine. Furthermore, indomethacin completely abolished the long-lasting contractions induced by transmural stimulation, noradrenaline, and ATP, but did not significantly affect the response to prostaglandin E2. The results indicate that the long-lasting contraction induced by transmural stimulation is mediated through prostaglandins release which may be triggered by neuro-transmitters or by endogenous substances.
Tetrodotoxin
Phentolamine
Guanethidine
Cite
Citations (5)
Adrenomedullin
Amylin
Amyloid (mycology)
Cite
Citations (7)
ABSTRACT The mechanical properties of the longitudinal and circular muscles of the earthworm, Pheretima communissima, were studied in various solutions. In the longitudinal muscle, field stimulation elicited two distinct waves of tension development, i.e. phasic and tonic contractions. But in the circular muscle, these components were not distinguishable. The phasic contraction in the longitudinal muscle increased in sodium-free (tris) solution while the tonic contraction was abolished. Neither the phasic nor the tonic contraction, however, was influenced by tetrodotoxin (3×10−8 M), d-tubocurarine (1·4 × 10−s M), or atropine (3·5 × 10−5 M). The contraction in the circular muscle was suppressed in sodium-free solution and also by tetrodotoxin (3×10−8 M), but was not affected by d-tubocurarine (1·4 × 10−;5 M) or by atropine (3·5 × 10−8 M). It is speculated that the phasic contraction of the longitudinal muscle is triggered by a calcium spike, and the contraction in the circular muscle is preceded by a sodium spike in muscle fibres.
Tonic (physiology)
Tetrodotoxin
Cite
Citations (25)
【Objective】To study the expression of pulmonary calcitonin gene-related peptide(CRGP) after reconstruction of left bronchus and its mechanism.【Methods】Thirty male Sprague Dawley rats were randomly divided into three groups according to the time of sampling: groups at 1 week,1 month and 3 months after reconstruction of left bronchus with 10 animals in each.Another 10 normal rats without reconstruction of bronchus were taken as normal control.Serum concentration of CGRP was detected by radio-immunity analysis method.The level of expression of CGRP mRNA was measured by RT-PCR method.【Results】Serum concentration of CGRP at 1 week and 1 month after reconstruction of left bronchus was significantly decreased than that in the normal control(P0.01) and gradually increased nearly to the normal level in 3 months after surgery.The expression of CGRP mRNA at 1 week and 1 month after reconstruction of left bronchus was significantly higher than that in the normal control(P0.01) and gradually declined to the normal level after 3 months(P0.05).【Conclusion】Serum concentration of CGRP and expression of CGRP mRNA are significantly changed after reconstruction of bronchus.It indicates that the expression of CGRP mRNA and the secretion of CGRP are dominated and regulated by CGRP-immunoreactive(IR) fibers.Meanwhile, CGRP may be as a local regulatory factor to stimulate endothelium hyperplasia and participate in damage and repair of airway.
Cite
Citations (0)