Involvement of calcium channels in the contractile activity of neurotensin but not acetylcholine: studies with calcium channel blockers and Bay K 8644 on the rat fundus

Donoso, M. Verónica; Huidobro‐Toro, J. Pablo; Kullak, A.

doi:10.1111/j.1476-5381.1986.tb16257.x

Cited by 16 publications

(3 citation statements)

References 19 publications

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“…This sustained increase in [Ca 2+ ]i results from an influx of extracellular calcium, which remains active as long as the stimulation with the peptide is maintained . Numerous stud-2523 ies have reported a role of extracellular calcium in the physiological effects of NT, for instance, in the release of prolactin (Memo et al, 1986) or the contraction of the rat fundus (Donoso et al, 1986) . In these two examples, it was suggested that NTRs were coupled to voltage-or receptor-operated calcium channels, but experimental evidence for that coupling is still lacking .…”

Section: Discussionmentioning

confidence: 99%

Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Hermans¹,

Gailly

Gillis

et al. 1995

Journal of Neurochemistry

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Transfected Chinese hamster ovary cells were used as a model for the study of the desensitization of the neurotensin receptor at the second messenger level. Stimulation with nanomolar concentrations of neurotensin elicited rapid rises in the cytosolic calcium concentration ([Ca2+]i), which remained elevated throughout the peptide application. A significant response was already detected with neurotensin concentrations as low as 0.01 nM. This high efficiency of neurotensin in mediating this calcium response contrasts with the nanomolar affinity of the peptide for its receptor measured in binding experiments. Evidence indicated that the initial elevation of the [Ca2+]i resulted from release of Ca2+ from intracellular stores, whereas the sustained response involved an influx of extracellular origin. Return to the basal level was only reached after extensive washing of the peptide or its displacement with the neurotensin receptor antagonist SR48692. After washing, further stimulations were still able to mediate an increase in the [Ca2+]i, indicating an apparent absence of rapid desensitization of the intracellular signaling pathway that mediates calcium mobilization. In contrast with this absence of response desensitization, the neurotensin receptors were found to internalize after stimulation with the peptide. This internalization was maximal after 30 min and accounted for ∼70% of the number of neurotensin binding sites located at the cell surface. These results indicate that despite the functional properties of the rat neurotensin receptor present in Chinese hamster ovary cells after transfection, the intracellular signaling pathway triggered by stimulation with neurotensin seems to be resistant to desensitization. This might be related to the high efficiency of the intracellular signaling pathway coupled to the neurotensin receptor observed in these cells. A possible absence of desensitization of the neurotensin receptor itself is also discussed.

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Section: Discussionmentioning

confidence: 99%

Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Hermans¹,

Gailly

Gillis

et al. 1995

Journal of Neurochemistry

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“…In this type of smooth muscle, membrane depolarization can increase the discharge rate of propagated action potentials leading to Ca entry through voltage-dependent Ca channels without causing depolarization block and thus it is effective in producing tension. The contractile activity of neurotensin in the rat fundus is sensitive to nifedipine and related calcium channel blockers, and it has been suggested that it may be coupled to voltage-dependent calcium channels (Donoso et al, 1986). …”

Section: Discussionmentioning

confidence: 99%

Membrane potential and current responses to neurotensin in the longitudinal muscle of the rectum of the fowl

Komori

Matsuoka

Kwon

et al. 1992

British J Pharmacology

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1The effects of neurotensin (NT) on membrane potential and membrane current of the longitudinal smooth muscle of chicken rectum were investigated by intracellular recording and whole-cell voltage clamp. 2 NT (3 nM-1.2 SAM), when applied via the bathing medium, produced a concentration-dependent membrane depolarization with an EC50 of 18 ± 2 nM (n = 7) which was accompanied by an increase in the membrane conductance. The effect was biphasic: an initial, rapid depolarization reached a peak within 2-3 min and then declined to a lower but still elevated level which was sustained until washout. 3 Excitatory junction potentials (ej.ps), which were non-adrenergic non-cholinergic (NANC) in nature, were decreased in amplitude and total duration in the presence of NT (0.6 jLM). The depression of the e.j.p. was due mainly to the reduction of the membrane resistance. 4 When NT was applied locally by means of pressure ejection from a micropipette containing NT, some cells responded with a membrane depolarization and some failed to respond, whereas ej.ps could invariably be elicited from all of them. 6 The present results suggest that the membrane depolarization, which may arise from activation of non-selective cation channels, and release of calcium from internal stores produced by neurotensin are responsible for its contractile activity in the longitudinal smooth muscle of chicken rectum. Further, the depolarizing effect may provide support for the involvement of NT in the NANC transmission in this preparation.

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“…The tension fading results from a depolarization block of action potential discharge, which seems to be especially important in the longitudinal muscle, a freely spiking smooth muscle (Komori & Ohashi, 1982), and from a time-and voltage-dependent inactivation of voltage-sensitive Ca channels (Hurwitz, 1986). On the basis of this idea, the reduction in the responses to bovine neurotensin and high K+, which both activate mainly voltage-sensitive Ca channels (Donoso et al, 1986;Ohashi & Komori, unpublished observations), can be explained. Furthermore, the prolonged increase in membrane conductance is a problem when explaining the inhibition of ej.ps.…”

Section: Discussionmentioning

confidence: 98%

Effects of prolonged exposure to α,β‐methylene ATP on non‐adrenergic, non‐cholinergic excitatory transmission in the rectum of the chicken

Komori

Kwon

Ohashi

1988

British J Pharmacology

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1 Effects of prolonged exposure to a,#-methylene ATP (a,f3-Me ATP) on contractions and excitatory junction potentials (ej.ps) evoked by non-adrenergic, non-cholinergic (NANC) excitatory nerve stimulation have been investigated in the chicken isolated rectum and longitudinal muscle strip from chicken rectum pretreated with atropine (0.5 gM), methysergide (2 Mm) and pyrilamine (3 gM).2 xf,#-Me ATP (20 nM-4 Mm) caused a rapid rise in tension of the longitudinal muscle of the isolated rectum preparation which returned to the baseline levels after a few minutes. The magnitude of the contractile response to NANC nerve stimulation was reduced after exposure to the drug. The inhibitory effect was related to the drug concentration; at 4 gM the nerve-mediated contraction was abolished and frequently converted to a relaxation.3 Adenosine 5'-triphosphate (ATP, 100MM), bovine neurotensin (2.5nM) and K+-rich solutions (30mM and 60mM) all produced a transient contraction of the isolated rectum preparation. The exposure to a,fl-Me ATP (0.2 and 4pM) also rendered the preparation less sensitive to these stimulant substances. 4 a,fl-Me ATP (0.2 and 4 gM) caused a membrane depolarization in cells of the longitudinal muscle strip. The depolarization reached a peak within 2-3 min after application and then decayed to a steady level that was still more positive than the baseline level. The electrotonic potentials were reduced in amplitude to 44 + 8% (n = 7) of the normal amplitude if measured at the peak depolarization produced with 0.2pM a,#-Me ATP, and to 62 + 10% (n = 7) if measured at the steady-state depolarization. With 4pM, the corresponding percentages were 33 + 7% (n = 8) and 55 + 7% (n = 8), indicating a decrease in membrane resistance. 5 The ej.ps in response to field stimulation of the intramural nerves and Remak's nerve stimulation were decreased in amplitude and duration during exposure to a,fi-Me ATP (0.2 and 4 gM).6 The smooth muscle cells regained normal membrane resistance and sensitivity to ATP on washout of a,,B-Me ATP (4 gM) more rapidly than the responses to NANC nerve stimulation.7 It can be argued from the results that the suppression by a,fi-Me ATP of the contraction and ej.p. evoked by NANC nerve stimulation in the chicken rectum, unlike the mammalian preparations described previously, is due mainly to a change in the electrical properties of the membrane of the smooth muscle cells, rather than being due, or only partly due, to desensitization of the purine receptor.

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Involvement of calcium channels in the contractile activity of neurotensin but not acetylcholine: studies with calcium channel blockers and Bay K 8644 on the rat fundus

Cited by 16 publications

References 19 publications

Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Membrane potential and current responses to neurotensin in the longitudinal muscle of the rectum of the fowl

Effects of prolonged exposure to α,β‐methylene ATP on non‐adrenergic, non‐cholinergic excitatory transmission in the rectum of the chicken

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Involvement of calcium channels in the contractile activity of neurotensin but not acetylcholine: studies with calcium channel blockers and Bay K 8644 on the rat fundus

Cited by 16 publications

References 19 publications

Lack of Rapid Desensitization of Ca2+ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Lack of Rapid Desensitization of Ca2+ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Membrane potential and current responses to neurotensin in the longitudinal muscle of the rectum of the fowl

Effects of prolonged exposure to α,β‐methylene ATP on non‐adrenergic, non‐cholinergic excitatory transmission in the rectum of the chicken

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Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization

Lack of Rapid Desensitization of Ca²⁺ Responses in Transfected CHO Cells Expressing the Rat Neurotensin Receptor Despite Agonist‐Induced Internalization