Different tachykinin receptor subtypes are coupled to the phosphoinositide or cyclic AMP signal transduction pathways in rat submandibular cells

Laniyonu, Adebayo; Sliwinski-Lis, Eva; Fleming, Norman

doi:10.1016/0014-5793(88)80365-x

Cited by 48 publications

(22 citation statements)

References 16 publications

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“…We focused on receptors coupled to G q proteins that release Ca 21 via phospholipase C and IP 3 -mobilization (Laniyonu et al, 1988;Lucaites et al, 1996;Ramsdell and Tashjian, 1986). Immunostaining identified NK1, 5-HT 2a , and TRH receptors (which stimulate G q -dependent Ca 21 signaling) not only on VRG astrocytes but also on neurons.…”

Section: Oligodendrocytes and Neurons Do Notmentioning

confidence: 99%

Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice

Härtel

Schnell

Hülsmann

2008

Glia

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A controlled, periodic exchange of air between lungs and atmosphere requires a neuronal rhythm generated by a network of neurons in the ventral respiratory group (VRG) of the brainstem. Glial cells, e.g. astrocytes, have been shown to be supportive in stabilizing this neuronal activity in the central nervous system during development. In addition, a variety of neuromodulators including serotonin (5-HT), Substance P (SP), and thyrotropin-releasing hormone (TRH) stimulate respiratory neurons directly. If astrocytes in the VRG, like their neuronal neighbors, are also directly stimulated by neuromodulators, they might indirectly affect the respiratory neurons and consequently the respiratory rhythm. In the present study, we provide support for this concept by demonstrating expression of NK1-R, TRH-R, and 5-HT(2)-R in astrocytes of the VRG with immunohistochemistry. Additionally, we showed that the external application of the neuromodulators 5-HT, SP, and TRH activate calcium transients in VRG astrocytes. Consequently, we postulate that in the VRG of the neonatal mouse, neuromodulation by SP, TRH, and serotonin also involves astrocytic calcium signaling.

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Section: Oligodendrocytes and Neurons Do Notmentioning

confidence: 99%

Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice

Härtel

Schnell

Hülsmann

2008

Glia

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“…Activation of NK1R couples to G q proteins (14,53), as well as G s (15) and G i and G z (16,54). G q is an important mediator of NK1R activation and leads to activation of PLC that causes phosphatidylinositol 4,5-bisphosphate cleavage to diacylglycerol and IP 3 (53).…”

Section: Discussionmentioning

confidence: 99%

“…NK1R triggers inhibition of adenylyl cyclase production via the pertussis toxin-sensitive G i protein in rat submandibular cells (16), and G z , which belongs to the G i family, couples to NK1R in Sf9 cells (54). However, G i proteins do not play any role in signaling downstream of NK1R in HEK293 cells, because treatment with pertussis toxin, which inhibits G i proteins, including G z , had no effect on cell shape change or bleb formation (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, NK1R has the ability to induce adenylyl cyclase activation and production of cAMP via the G s protein, although the potency of the NK1R agonists in generating cAMP accumulation is lower as compared with their ability to induce IP 3 formation and intracellular calcium increase (15). Furthermore, NK1R was also linked to inhibition of adenylyl cyclase production via the pertussis toxin-sensitive G i protein in rat submandibular cells (16). G protein-independent coupling mechanisms initiated by neurokinin receptors have also been suggested, especially in connection with ion channels (17).…”

Section: Neurokinin 1 Receptor (Nk1r)mentioning

confidence: 99%

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Neurokinin 1 Receptor Mediates Membrane Blebbing in HEK293 Cells through a Rho/Rho-associated Coiled-coil Kinase-dependent Mechanism

Meshki

Douglas

Lai

et al. 2009

Journal of Biological Chemistry

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We have investigated the effect of neurokinin 1 receptor (NK1R) agonists on HEK293 cells transfected with the NK1R receptor. The NK1R receptor mediates dramatic shape changes that include contractions of the membrane cortex resulting in membrane bleb formation. We have found that the cell shape changes correlate with changes in electrical impedance measured in cellular monolayers. The shape and impedance changes were prevented after preincubation with NK1R antagonists aprepitant and L-73060. Although bleb formation usually heralds apoptotic cell death, we have found that NK1R-mediated cellular blebbing does not associate with apoptosis. Preincubation with a cell-permeable derivative of C3 transferase that blocks Rho or with the Rho-associated coiled-coil kinase inhibitor Y27632 completely prevented NK1R-induced shape and impedance changes. Blebbing was also completely inhibited by ML-9, a myosin light chain kinase inhibitor. Furthermore, the phospholipase C inhibitor U73,122 did not interfere with the effect of Substance P (SP) on cellular morphology and cellular impedance but completely blocked SP-induced intracellular calcium increase, indicating that the blebbing is a process independent of intracellular calcium elevations. Blebbing is a protein kinase C-independent process, since the nonselective protein kinase C inhibitor GF109203X did not interfere with SP-induced effects. Based on these results, we provide the first evidence that NK1R receptorligand interaction can cause apoptosis-independent cellular blebbing and that this process is mediated by the Rho/Rho-associated coiled-coil kinase pathway.

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“…It combines with and activates muscarinic receptors that evoke secretion of large quantities of serous fluid [1]. Substance P has also been found in the parasympathetic nerves, colocalized with acetylcholine, and it also evokes copious salivary secretion by activating tachykinin 1 (K1) receptors [2]. Since nitric oxide synthase (NOS) has been found to control the function of many organs of the body by its distribution in the non-adrenergic, non-cholinergic branch of the autonomic nervous system [3], we hypothesized that it might play a role in salivary secretion.…”

Section: Introductionmentioning

confidence: 99%

Role of Nitric Oxide in Salivary Secretion

Lomniczi

Suburo

Elverdín

et al. 1998

Neuroimmunomodulation

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Since nitric oxide has been found to control the function of many organs of the body by the non-adrenergic, non-cholinergic branch of the autonomic nervous system, we hypothesized that it might play a role in salivary secretion. Therefore, we investigated the distribution of nitric oxide synthase (NOS) throughout the submaxillary gland and also studied the ability of inhibitors of NOS to interfere with salivation induced by a cholinergic agonist, metacholine, and by a polypeptide, substance P. The secretory responses were determined in rats anesthetized with chlorolose following intravenous injection of the various pharmacological agents. There was no basal flow of saliva and dose-response curves were obtained by sequential intravenous injection of increasing doses of the drugs. Then, in the same animal, the same dose-response curves were performed in the presence of NOS inhibitors. L-Nitro-arginine-methyl-ester (L-NAME; 20 mg/kg) produced an over 50% inhibition of the dose-related salivation induced by metacholine. Similar results were produced with L-N^G-monomethyl-L-arginine (L-NMMA; 5 mg/kg). The salivation induced by much lower molar doses of substance P was dramatically greater than that obtained with metacholine. The response to substance P was almost completely inhibited by L-NMMA at the lowest dose (0.3 mg/kg), but at higher doses (1 mg/kg), the inhibition was only around 60% and at the highest dose (3 mg/kg) only about 20%. In control rats, there were roughly equal amounts of calcium-dependent and calcium-independent NOS in the gland at this time. At the end of the experiment, the effect of the inhibitor of NOS, L-NMMA, on the NOS activity in the submandibular gland was determined. At this time, the Ca²⁺-dependent NOS was decreased and the Ca²⁺-independent NO was increased. The prior injection of L-NMMA reduced calcium-dependent NOS activity by approximately 70% but calcium-independent activity by only 30%. These results indicate that, at least at the end of the experiment, the blockade of NOS imposed by NMMA was incomplete. This could account in part for the failure of the inhibitors to block completely the stimulatory effect of the two secretagogues. Analysis of the distribution of NOS in the salivary gland revealed that it was not present in the acinar cells, but in neural terminals within the gland and also in the ductile system which contained neural (n) NOS in the apical membrane of the excretory and striated ducts, the cytoplasm of granular convoluted tubules and, to a lesser extent, in the cytoplasm of excretory and striated ducts. Macrophage (inducible) NOS was also found not only in the macrophages, but also in the tubules and ducts. Since drugs were used that would act on the receptors in the gland, the role of NO in our conditions is probably mediated by nNOS and iNOS in the ductile and tubular structures. Since iNOS would already be active, it is unlikely to play a role in this acute secretory activity. Rather the nNOS in these non-neural cells is probably ac...

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Different tachykinin receptor subtypes are coupled to the phosphoinositide or cyclic AMP signal transduction pathways in rat submandibular cells

Cited by 48 publications

References 16 publications

Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice

Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal mice

Neurokinin 1 Receptor Mediates Membrane Blebbing in HEK293 Cells through a Rho/Rho-associated Coiled-coil Kinase-dependent Mechanism

Role of Nitric Oxide in Salivary Secretion

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