Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells.
This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.
Corleto
V D
VD
Department of Digestive and Liver Diseases, 1st and 2nd Schools of Medicine, University 'La Sapienza', Rome, Italy. corleto@bce.uniroma1.it
Severi
C
C
Romano
G
G
Tattoli
I
I
Weber
H C
HC
Stridsberg
M
M
Rindi
G
G
Campanini
N
N
Tomassoni
F
F
Pagotto
U
U
Coy
D H
DH
Jensen
R T
RT
Delle Fave
G
G
D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
C110577:CH 288; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D015282:Octreotide