Activation of neuronal SST₁ and SST₂ receptors decreases neurogenic secretion in the guinea-pig jejunum.
BACKGROUND
Vasoactive intestinal peptide (VIP) submucosal neurons, the main regulators of gut secretion, display inhibitory postsynaptic potentials mediated by somatostatin (SOM) acting on SST(1) and SST(2) receptors (SSTR(1), SSTR(2)) in the guinea-pig small intestine. We investigated the implications of this for neurally-evoked mucosal secretion.


METHODS
Mucosal-submucosal preparations from guinea-pig jejunum were mounted in Ussing chambers to measure Cl(-) secretion, measured by short circuit current (I(sc)). All drugs were added serosally. Veratridine (1 μmol L(-1)) was used to stimulate neurons and provide a robust secretory response for pharmacological testing.5-hydroxytrptamine (5-HT, 300 nmol L(-1)) was used to specifically activate non-cholinergic secretomotor neurons, while 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 μmol L(-1)) was used to stimulate all secretomotor neurons.


RESULTS
Somatostatin (50 nmol L(-1)) induced a tetrodotoxin (TTX, 1 μmol L(-1))-sensitive decrease in secretion. Somatostatin also reduced the veratridine-induced increase in I(sc). The effects of SOM were significantly reduced by blocking SSTR(1) and SSTR(2) individually or together. Blocking SSTR(1) abolished the inhibition produced by SOM. Quantitative PCR demonstrated that SSTR(1) and SSTR(2) were much more highly expressed in the submucosa than the mucosa. Submucosal SSTR(1) expression was several fold higher than SSTR(2). Responses to DMPP (biphasic) and 5-HT (monophasic) were TTX-sensitive. Somatostatin significantly reduced the 5-HT-induced increase in I(sc), and the second, more sustained phase evoked by DMPP.


CONCLUSIONS
These data suggest that SOM exerts its antisecretory effects by suppressing firing of VIP secretomotor neurons, rather than via a direct action on mucosal enterocytes.
Foong
J P P
JP
Department of Anatomy & Cell Biology, University of Melbourne, Parkville, Victoria, Australia. jpfoong@unimelb.edu.au
Parry
L J
LJ
Bornstein
J C
JC
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006168:Guinea Pigs; D007583:Jejunum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002712:Chlorides; D018722:Nicotinic Agonists; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D012701:Serotonin; D013779:Tetrodotoxin; D013004:Somatostatin; D004246:Dimethylphenylpiperazinium Iodide; D012313:RNA; D014701:Veratridine; C093733:somatostatin receptor 2