This FIRCA application provides a new direction for the parent grant """""""" Modulation of Muscarinic Responses by Inositol Lipids"""""""". The goal of the parent grant is to study the coupling of muscarinic receptor subtypes to second messenger signal transduction pathways using transfected cells. In the present study, muscarinic receptor subtypes and the second messenger pathways activated by them will be identified in guinea pig gallbladder smooth muscle. The applicant proposes a rather classical pharmacological approach, correlating receptor binding with functional studies. Muscarinic subtypes will be identified by competitive antagonist binding using classical and novel antagonists, antagonist inhibition of receptor-mediated contraction will be determined, and measurement of second messengers cAMP and PI metabolites following receptor activation. In addition mRNA hybridization techniques will be used to evaluate genetic expression of muscarinic subtypes. The applicant suggests that the information gleamed from these studies will contribute to the development of selective agents to be used in cases of gallbladder spasm.
| Cabadak, Hulya; Cuadra, Adolfo E; El-Fakahany, Esam E et al. (2009) M2, M3, and M4 muscarinic receptors are expressed in the guinea pig gallbladder. J Recept Signal Transduct Res 29:63-6 |
| Akici, A; Karaalp, A; Iskender, E et al. (2000) Further evidence for the heterogeneity of functional muscarinic receptors in guinea pig gallbladder. Eur J Pharmacol 388:115-23 |
| Akici, A; Karaalp, A; Skender, E et al. (1999) Muscarinic M(2) receptors are not primarily involved in the contraction of guinea-pig gallbladder smooth muscle. Pharmacol Res 40:443-9 |
| Oktay, S; Cabadak, H; Iskender, E et al. (1998) Evidence for the presence of muscarinic M2 and M4 receptors in guinea-pig gallbladder smooth muscle. J Auton Pharmacol 18:195-204 |
