Cholinergic stimulation of amylase secretion from pancreatic acinar cells studied with muscarinic acetylcholine receptor mutant mice.

Muscarinic acetylcholine receptors (mAChRs) expressed by pancreatic acinar cells play an important role in mediating acetylcholine-dependent stimulation of digestive enzyme secretion. To examine the potential roles of M(1) and M(3) mAChRs in this activity, we used M(1) and M(3) receptor single knockout (KO) and M(1)/M(3) receptor double KO mice as novel experimental tools. Specifically, we examined the ability of the muscarinic agonist carbachol to stimulate amylase secretion in vitro, using dispersed pancreatic acini prepared from wild-type and mAChR mutant mice.

Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice.

Identification of the specific muscarinic acetylcholine receptor (mAChR) subtypes mediating stimulation of salivary secretion is of considerable clinical interest. Recent pharmacological and molecular genetic studies have yielded somewhat confusing and partially contradictory results regarding the involvement of individual mAChRs in this activity. In the present study, we re-examined the roles of M(1) and M(3) mAChRs in muscarinic agonist-mediated stimulation of salivary secretion by using M(1) and M(3) receptor single-knockout (KO) mice and newly generated M(1)/M(3) receptor double-KO mice.

Location of the actual signal in the negatively charged leader sequence involved in the import into the mitochondrial matrix space.

Proteins destined for the mitochondrial matrix space have leader sequences that are typically present at the most N-terminal end of the nuclear-encoded precursor protein. The leaders are rich in positive charges and usually deficient of negative charges. This observation led to the acid-chain hypothesis to explain how the leader sequences interact with negatively charged receptor proteins.

The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate.

The critical steps in bile acid metabolism have remarkable differences between humans and mice. It is known that human cholesterol 7 alpha-hydroxylase, the enzyme catalyzing the rate-limiting step of bile acid synthesis, is more sensitive to bile acid suppression. In addition, hepatic bile acid export in humans is more dependent on the bile salt export pump (BSEP).