Urocortin 1 inhibits guinea pig gallbladder contractility in vitro via corticotropin-releasing factor receptor 2.
In this study, we tested the effect of urocortin 1 (Ucn1) on the contractility of gallbladder smooth muscle (GBSM) strips from guinea pigs and studied the involvement of corticotropin-releasing factor (CRF) receptors in this effect. The effect of Ucn1 on the isometric contractions of non-contracted and acetylcholine (Ach)-contracted GBSM, and the effects of CRF-R antagonists antalarmin and astressin 2B on the effect of Ucn1 were studied. In addition, the expression of receptors for CRF-R1 and CRF-R2 in guinea pig gallbladder were investigated using reverse transcription - polymerase chain reaction (RT-PCR). Ucn1 dose-dependently inhibited the contractility of GBSM. Moreover, Ucn1 decreased the resting tension, the mean contractile amplitude, and the contractile frequency in both non-contracted and Ach-contracted strips of GBSM. Furthermore, Ucn1 induced rightward shift of the Ach concentration-response curve of Ach in Ach-contracted strips. This inhibitory effect of Ucn1 on both non-contracted and Ach-contracted strips was inhibited by astressin 2B, but not by antalarmin. RT-PCR demonstrated that the CRF-R2, but not CRF-R1 receptor subtype is expressed in the muscularis muscle of guinea pig gallbladder. In conclusion, Ucn1 has an inhibitory effect on the contractility of GBSM of guinea pig, mediated through stimulating CRF-R2 receptors in GBSM. More studies are needed to clarify the intracellular signaling events involved in this effect.
Department of Physiology, College of Medicine, Najran University, Saudi Arabia.
Samy M
SM
Abd El-Aziz
Basel A
BA
Abdel-Wahab
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D018076:DNA, Complementary / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054832:Urocortins / Q000032:analysis / Q000502:physiology*
C101531:CRF receptor type 2; D018076:DNA, Complementary; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C103016:antalarmin; C528574:astressin-2B; D000109:Acetylcholine