Preventive effects of parathyroid hormone-related peptide on stress-induced gastric hypercontraction in the rat.
OBJECTIVE
Parathyroid hormone-related peptide (PTHrP) appears to be a potent smooth muscle relaxant, but there has been no study of its effects on gastric motility in vivo. The purposes of this study were to evaluate the effects of external PTHrP on stress-induced gastric motility in vivo and on the expression of PTHrP and PTH/PTHrP receptors in the rat stomach.


METHODS
Stress-induced hypercontraction was evoked by restraint water immersion (RWI). Gastric motility was evaluated with a strain gauge force transducer, and the effects of external PTHrP-(1-34) (10 micro i.p.) on gastric motility were examined. Expressions of PTHrP and PTH/PTHrP receptor mRNA were evaluated by RNase protection assay.


RESULTS
External PTHrP significantly suppressed abnormal contraction and mucosal lesions upon RWI stress. Upon RWI stress, the expression of PTHrP mRNA decreased, but that of PTH/PTHrP receptor mRNA was enhanced reciprocally. The PTH/PTHrP receptor was localized in smooth muscle cells of the muscle layers immunohistochemically.


CONCLUSIONS
These findings suggest that smooth muscle contractile activity is modified by the autocrine/paracrine mechanism of PTHrP in the rat stomach and that the external PTHrP prevents stress-induced hypercontraction and mucosal lesions.
Ito
Masahiro
M
Department of Pathology, Clinical Research Center, National Nagasaki Medical Center, Omura, Japan. itohm@nmc.hosp.go.jp
Nakashima
Masahiro
M
Nakayama
Toshiyuki
T
Shikuwa
Saburo
S
Ohtsuru
Akira
A
Sekine
Ichiro
I
D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone