Somatostatin inhibits adrenergic and cholinergic neurotransmission in smooth muscle

Cohen, Marlene L.; Rosing, E L; Wiley, Kathryn S.; Slater, Irwin H.

doi:10.1016/0024-3205(78)90463-0

Cited by 82 publications

(23 citation statements)

References 9 publications

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“…It has also been suggested that somatostatin is released from nerve terminals of postganglionic sympathetic neurones and acts on nerve terminal receptors to inhibit the release of noradrenaline (Cohen, Rosing, Wiley & Slater, 1978). If one assumes that voltage-gated Ca2+ currents, with properties similar to those found on the soma, are also located on the nerve terminals, then the decrease in Ca2+ current induced by somatostatin observed in this study could affect the release of noradrenaline.…”

Section: Functional Implicationsmentioning

confidence: 57%

Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.

Ikeda

Schofield

1989

The Journal of Physiology

173

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SUMMARY1. The effects of somatostatin and somatostatin analogues on a Ca2+ current from acutely isolated and short-term (24-48 h) cultured adult rat superior cervical ganglion (SCG) neurones were studied using the whole-cell variant of the patchclamp technique.2. Somatostatin (SOM) produced a rapid, reversible and concentrationdependent reduction of the Ca2+ current. Ca2+ current amplitude was reduced over the voltage range -15 to + 40 mV with the greatest reduction occurring where the amplitude was maximal (ca + 10 mV). In the presence of SOM, the Ca2+ current rising phase was slower and biphasic at potentials between 0 and +40 mV.3. Application of 0 1 ,tM-SOM for greater than 10 s resulted in a desensitization of the response. During a 4 min application of 01I aM-SOM, Ca2+ current amplitude returned to about 90 % of control. A second application of 0 1 ,IM-SOM produced less block than the initial application.4. Concentration-response curves for SOM, somatostatin-14 (SOM-14) and somatostatin-28 (SOM-28) were fitted to a single-site binding isotherm. The concentrations producing half-maximal block and the maximal attainable blocks of the Ca2+ current for SOM, SOM-14 and SOM-28 were 3 3, 5 4 and 35 nm, respectively and 55, 51 and 54%, respectively. SOM-14 and SOM-28 slowed the Ca2+ current rising phase in a manner similar to that of SOM. Somatostatin-28[1 12] had no effect on the Ca2+ current at 1 JIM. S. R. IKEDA AND G. G. SCHOFIELD significantly less block of Ca2+ current amplitude (7-1 and 14-7 %, respectively) when compared with controls.7. Internal dialysis with solutions containing 500 /M-guanosine-5'-0-(2-thiodiphosphate)(GDP-,8-S) had no significant effect on either the Ca21 current amplitude or block produced by 01 ,sM-SOM.8. Internal dialysis with solutions containing 500 /LM-cyclic adenosine 3',5'-monophosphate (cyclic AMP) and 3-isobutyl-1-methylxanthine had no significant effect on either the Ca2+ current block produced by 0-1 /tM-SOM or the Ca2+ current amplitude. 9. Treatment of SCG neurones in short-term culture with 200 ng/ml pertussis toxin (PTX) for 12-16 h greatly reduced the ability of 01 #,M-SOM to produce Ca2+ current block. Mean Ca2+ current block was 4-9 and 40-8% for PTX-treated and control cultures; respectively. 10. These results suggest that somatostatin blocks a Ca2+ current in adult rat SCG neurones via a pertussis toxin-sensitive guanine nucleotide regulatory protein. This effect appears to be independent of intracellular cyclic AMP.

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Section: Functional Implicationsmentioning

confidence: 57%

Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.

Ikeda

Schofield

1989

The Journal of Physiology

173

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“…The generalized inhibitory effect of somatostatin could, for example, be explained if the mechanism of releasing autonomic nervous transmitter substances and for releasing hormones is similar and so susceptible to inhibition by the same substance or, if somatostatin inhibits hormone release, by its inhibitory effects on neurotransmission (Cohen et al 1978). On the other hand it is difficult to explain in this way the different actions ascribed to a hormone like gastrin.…”

Section: Investigative Problemsmentioning

confidence: 99%

“…Subsequently, this peptide was found in larger quantities in the gastrointestinal tract (Arimura et al 1975;Pol& et al 1975) and was shown to inhibit the release of many other hormones such as insulin, glucagon and gastrin in addition to having a direct inhibitory effect on acid secretion by the parietal cells of the stomach (Gomez Pan et al 1975). There is also evidence that somatostatin is released from nerves (Uvnas-Wallenstein et al 1977;Iversen et al 1978) and that in turn it may inhibit the release of adrenergic and cholinergic transmitter substances (Guillemin, 1976;Cohen et al 1978).…”

Section: Investigative Problemsmentioning

confidence: 99%

Hormones and metabolism: a background

Blair

1983

Proc. Nutr. Soc.

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“…The ability of SS14 to inhibit neurogenically mediated contractions in a range of isolated smooth muscle preparations is well documented (Cohen et al, 1978;Furness & Costa, 1979;Magnam et al, 1979;McIntosh et al, 1986;Priestley & Woodruff, 1988). However, the somatostatin receptors mediating these inhibitory actions remain poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

Feniuk

Dimech

Humphrey

1993

British J Pharmacology

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1 Somatostatin14 (SS14) inhibits neurogenically mediated contractile responses in guinea-pig ileum and vas deferens and exerts a direct negative inotropic action in guinea-pig spontaneously beating right atrium. In this study, the receptors mediating these inhibitory effects have been characterized by comparing the potencies of several cyclic somatostatin analogues. 2 In the guinea-pig ileum, SS14, somatostatin28 (SS28), somatostatin25 (SS25) and several smaller cyclic somatostatin analogues including octreotide, angiopeptin and CGP 23996, inhibited neurogenically mediated contractile responses, each being of similar potency. 3 In contrast, in the guinea-pig vas deferens and right atrium, SS28 was about 30 times more potent than SS14. However, although angiopeptin was nearly as potent as SS14 as an agonist in the vas deferens, in guinea-pig atrium angiopeptin had low intrinsic activity and antagonized the negative inotropic action of both SS14 and SS28 (pKB values of 7.4 and 7.2, respectively). CGP 23996 was 2-7 times weaker than SS14 in guinea-pig vas deferens and atria.4 Phosphoramidon (1 AM) and amastatin (10 JAM) did not influence the potency of SS14 or SS28 in either the guinea-pig ileum or right atrium. In the guinea-pig vas deferens, phosphoramidon and amastatin did not affect the potency of SS28, but enhanced the potency of SS14 about 5 fold. Despite the presence of phosphoramidon and amastatin, SS28 was still more potent than SS14 in the vas deferens. 5 The putative somatostatin receptor blocking drug, cyclo(7-aminoheptanoyl Phe-D-Trp-Lys-Thr[Bzl]) (CPP; 1 JAM), did not antagonize the effects of either SS14 or SS28 in ileum, vas deferens or atrial preparations. 6 Somatostatin14 did not modify the contractile action of carbachol or ax,-methylene ATP in the ileum and vas deferens respectively, suggesting that the site of the inhibitory effects on neurogenically mediated contractile responses in both preparations was pre-junctional. Consistent with this conclusion was the observation that the inhibitory effect of SS14 was markedly and inversely related to the external Ca2+ concentration. The inhibitory effect of SS14 in guinea-pig atrium was only partly dependent on the external Ca2+ concentration. 7 The somatostatin receptors mediating the inhibitory effect of SS14 in the ileum and vas deferens can be distinguished by the differential relative potencies of SS14 and SS28. In the former, SS14 and SS28 have similar potency whilst in the latter SS28 is much more potent. In this respect, the somatostatin receptor mediating negative inotropy in the guinea-pig right atrium appears similar to that identified in the vas deferens.8 We suggest that the somatostatin receptor mediating inhibition of neurogenic contraction in the ileum is similar to the recently cloned SSTR2 receptor. In contrast, the somatostatin receptor mediating negative inotropy in the atrium and inhibition of neurotransmission in the vas deferens appears similar to the SSTR4 receptor which recognises SS28 with higher affinity than SS14.

show abstract

Somatostatin inhibits adrenergic and cholinergic neurotransmission in smooth muscle

Cited by 82 publications

References 9 publications

Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.

Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.

Hormones and metabolism: a background

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

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