Somatostatin‐mediated inhibitory postsynaptic potential in sympathetically denervated guinea‐pig submucosal neurones.

Shen, Ke Zhong; Surprenant, Annmarie

doi:10.1113/jphysiol.1993.sp019878

Cited by 36 publications

(24 citation statements)

References 35 publications

(46 reference statements)

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“…Non-adrenergic slow IPSPs in response to repetitive focal stimulation have also been described in the ileum (Bornstein et al 1988;Shen & Surprenant, 1993) and caecum (Mihara et al 1987;Mihara & Nishi, 1989). In this investigation, the occurrence of the non-adrenergic slow IPSP was found to be highly variable in all the regions studied, even during a single recording.…”

Section: Electrophysiological Classes Of Submucosal Neurones In the Gsupporting

confidence: 49%

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea‐pigs: comparisons with caecum and descending colon

Cunningham

Hirai²,

Mihara³

et al. 1997

Experimental Physiology

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SUMMARYA systematic examination has been made of' the active and passive electrophysiological properties and synaptic inputs of forty-four randomly impaled submucosal neurones in the proximal colon of the guinea-pig to compare these characteristics directly with those of submucosal neurones in the caecum (n = 70) and descending colon (n = 45). Within each of the three electrophysiological classes of submucosal neurones identified (S, S/AH and AH), no statistically significant regional differences were found with respect to the resting membrane potential, membrane time constant or input resistance between neurones of the proximal colon, descending colon and caecum. Of submucosal neurones from the proximal colon, forty-three of forty-four (98%) received fast excitatory synaptic potentials (fast EPSPs); thirty-nine (91 Oo) were S neurones and the others were S/AH neurones; only one of the forty-four cells (2 %) was an AH neurone. An idazoxan-sensitive slow inhibitory postsynaptic potential (slow IPSP) was induced in thirty of forty-three S and S/AH neurones (70 %) of the proximal colon, compared with sixty-one of sixty-six caecal neurones (92 %) and twelve of forty-one neurones (29'%) in the descending colon. The mean (+ S.E.M.) amplitude of the slow IPSP in proximal colonic neurones was 17 + 1 mV (range, 6-30 mV; n = 30), compared with the significantly larger synaptic response (25 + 1 mV; range, 7-38 mV; n = 66; P < 0.05) recorded in the caecum; the mean slow IPSP amplitude in the descending colon was significantly smaller (12 + 2 mV; range, 5-27 mV; n = 12; P < 0 05) than that in the caecum. In the proximal colon and caecum, only those neurones with a slow IPSP had a hyperpolarizing response to noradrenaline, whereas about 50 % of those neurones of the descending colon that lacked a slow IPSP were hyperpolarized by noradrenaline, acting via a2-adrenoceptors. Thus, the electrophysiological characteristics of the submucosal neurones of the proximal colon more closely resemble those of the caecum than those of the descending colon, of which many do not have a functional noradrenergic synaptic input. Furthermore, the results confirm that there are fundamental regional differences in the guinea-pig large intestine with respect to the synaptic organization of submucosal neurones of particular electrophysiological classes.

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Section: Electrophysiological Classes Of Submucosal Neurones In the Gsupporting

confidence: 49%

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea‐pigs: comparisons with caecum and descending colon

Cunningham

Hirai²,

Mihara³

et al. 1997

Experimental Physiology

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“…For example, in AtT-20 pituitary cells, PMA treatment did not alter SRIF activation of an inwardly rectifying potassium current, whereas cannabinoid CB1 receptor activation of this current was blocked (35). Similarly, phorbol esters did not alter SRIF-induced hyperpolarization in guinea pig submucosal neurons (36). These studies illustrate the capacity of protein kinase C to perturb the function of some, but not all, endogenous sst receptors and indicate that this kinase may have a role in the regulation of cellular responsiveness to SRIF.…”

Section: Figmentioning

confidence: 93%

Protein Kinase C Activation Stimulates the Phosphorylation and Internalization of the sst2A Somatostatin Receptor

Hipkin¹,

Wang

Schönbrunn

2000

Journal of Biological Chemistry

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The sst2A receptor is expressed in the endocrine, gastrointestinal, and neuronal systems as well as in many hormone-sensitive tumors. This receptor is rapidly internalized and phosphorylated in growth hormone-R2 pituitary cells following somatostatin binding (Hipkin, R. W., Friedman, J., Clark, R. B., Eppler, C. M., and Schonbrunn, A. (1997) J. Biol. Chem. 272, 13869 -13876). The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), also stimulates sst2A phosphorylation. Here we examine the mechanisms and consequences of PMA and agonist-induced sst2A phosphorylation. Like somatostatin, both PMA and bombesin increased sst2A receptor phosphorylation within 2 min. The PKC inhibitor GF109203X blocked PMA-and bombesin-stimulated sst2A phosphorylation, whereas stimulation by the somatostatin analog SMS 201-995 was unaffected. Agonist and PMA each stimulated phosphorylation in two receptor domains, the third intracellular loop and the C-terminal tail. Functionally, PMA dramatically increased the internalization of the sst2A receptor-ligand complex. This PMA stimulation was blocked by GF109203X, whereas basal internalization was unaffected. However, neither basal nor PMA-stimulated internalization was altered by pertussis toxin, whereas both were blocked by hypertonic sucrose. Therefore PKC activation and agonist binding stimulate sst2A phosphorylation by distinct mechanisms, and PKC potentiates internalization of the sst2A receptor via clathrin-coated pits. Thus, hormonal stimulation of PKC-coupled receptors may provide a mechanism for regulating the inhibitory actions of somatostatin in target tissue.For most G protein-coupled receptors, exposure to an agonist leads to a decrease in receptor responsiveness (homologous desensitization) often coincident with internalization of surface receptors (for reviews see Refs. 1 and 2). Additionally, agonistindependent or heterologous desensitization may occur when hormonal activation of one receptor reduces cellular responsiveness through a different receptor system (3). Whereas homologous desensitization may be mediated by either G proteincoupled receptor kinases (GRKs) 1 or second messengerdependent protein kinases, heterologous desensitization is thought to involve only the latter. GRKs preferentially phosphorylate the agonist-occupied receptor, increasing its affinity for cytoplasmic arrestins, which disrupt receptor G protein coupling and may also act as adaptors for receptor internalization via clathrin-coated pits. In contrast, heterologous desensitization can involve phosphorylation of unoccupied as well as agonist-occupied receptors and may or may not be associated with increased receptor internalization. The somatostatin peptides (SRIF-14 and SRIF-28) regulate endocrine, exocrine, immune, and neuronal function through binding to a family of six G protein-coupled receptors (sst1, sst2A, sst2B, sst3, sst4, and sst5) (4, 5). Expression of the SRIF receptor 2A subtype (sst2A) in the central nervous system (6), the pituitary (7), the endocrine and exocrin...

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“…(3) [92]. There is, however, a second component of this response, which is thought to be due to somatostatin [112], although the receptor subtype has not been identified. The second component is mimicked by local application of either somatostatin or enkephalin, but opioid antagonists do not block the idazoxan resistant IPSP in these neurons, while somatostatin desensitization does [112].…”

Section: Ipsps and Their Transmittersmentioning

confidence: 99%

“…3): one mediated via 2 -adrenoceptors [92] and the other apparently by somatostatin [112]. They are the only submucosal neurons to receive direct synaptic connections from sympathetic neurons and thus are an important regulatory target for control of whole body water and electrolyte balance.…”

Section: Secretomotor Pathwaysmentioning

confidence: 99%

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

Gwynne

Bornstein²

2007

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Digestion and absorption of nutrients and the secretion and reabsorption of fluid in the gastrointestinal tract are regulated by neurons of the enteric nervous system (ENS), the extensive peripheral nerve network contained within the intestinal wall. The ENS is an important physiological model for the study of neural networks since it is both complex and accessible. At least 20 different neurochemically and functionally distinct classes of enteric neurons have been identified in the guinea pig ileum. These neurons express a wide range of ionotropic and metabotropic receptors. Synaptic potentials mediated by ionotropic receptors such as the nicotinic acetylcholine receptor, P2X purinoceptors and 5-HT 3 receptors are seen in many enteric neurons. However, prominent synaptic potentials mediated by metabotropic receptors, like the P2Y 1 receptor and the NK 1 receptor, are also seen in these neurons. Studies of synaptic transmission between the different neuron classes within the enteric neural pathways have shown that both ionotropic and metabotropic synaptic potentials play major roles at distinct synapses within simple reflex pathways. However, there are still functional synapses at which no known transmitter or receptor has been identified. This review describes the identified roles for both ionotropic and metabotropic neurotransmission at functionally defined synapses within the guinea pig ileum ENS. It is concluded that metabotropic synaptic potentials act as primary transmitters at some synapses. It is suggested identification of the interactions between different synaptic potentials in the production of complex behaviours will require the use of well validated computer models of the enteric neural circuitry.

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Somatostatin‐mediated inhibitory postsynaptic potential in sympathetically denervated guinea‐pig submucosal neurones.

Cited by 36 publications

References 35 publications

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea‐pigs: comparisons with caecum and descending colon

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea‐pigs: comparisons with caecum and descending colon

Protein Kinase C Activation Stimulates the Phosphorylation and Internalization of the sst2A Somatostatin Receptor

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

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