Human circular colonic smooth muscle cells possess active somatostatin receptors.
OBJECTIVE
Somatostatin alters in vivo colonic motility in different species including humans. Few data are available on a cellular basis that could explain the effects of somatostatin on human colon motility. To address these issues we studied the effects of somatostatin on isolated human circular colonic smooth muscle cells to establish whether its actions are directly or neurally mediated.


METHODS
Circular smooth muscle cells were prepared by enzymatic digestion from surgical specimens of human colon (Sigma) and resuspended in HEPES buffer containing protease inhibitors.


RESULTS
Cholecystokinin (1 nM), carbachol (30 nM) and KCl (20 mM) each caused a contraction of 17%, 16.5% and 15%, respectively. 1 microM of either somatostatin-14, somatostatin-28 or SMS 201-995 alone were able to produce a contraction of 5.1%, 5.7%, and 6.8%, respectively. When smooth muscle cells were preincubated with each of the above-mentioned somatostatin analogs, cholecystokinin-mediated contraction was dose-dependently inhibited only in the presence of antiproteases. The half-maximal effective concentration (EC50) for somatostatin-14, somatostatin-28 and SMS 201-995 were similar (3.5, 5.6, 3.2 nM, respectively).


CONCLUSIONS
Somatostatin acts directly on human circular colonic smooth muscle cells through specific somatostatin receptors. SMS 201-995, a somatostatin receptor subtype-2 preferring analogue, shows a high affinity in inhibiting cholecystokinin-mediated contraction, suggesting the presence of somatostatin receptor subtype-2 on human circular colonic smooth muscle cells.
Corleto
V D
VD
Department of Human Biotechnology, La Sapienza University of Rome, Italy.
Romano
G
G
Severi
C
C
Annibale
B
B
Nasoni
S
S
Strom
R
R
Jensen
R T
RT
Delle Fave
G
G
D000368:Aged; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000187:drug effects*; D012016:Reference Values; D013004:Somatostatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D017481:Receptors, Somatostatin; D013004:Somatostatin; D011189:Potassium Chloride; D002217:Carbachol; D002766:Cholecystokinin