Effects of gestational age on prostaglandin EP receptor expression and functional involvement during in vitro contraction of the guinea pig uterus.

Prostaglandin E(2) (PGE(2)) exerts diverse biological effects through four G-protein-coupled cell surface receptor subtypes, EP1-4. This study's objective was to characterize EP1-4 receptor mRNA expression within pregnant guinea pig myometrium during early implantation stage (gestation day [GD] 6) and late stage gestation (GD 50) and evaluate in vitro contractile activity of receptor subtype selective agonists. Using RT-PCR, qualitative gene expression patterns of EP2, EP3, and EP4 mRNA were detected in the myometrium and remained unchanged between the gestational ages.

Inhibitory effects of antipsychotics on carbachol-enhanced insulin secretion from perifused rat islets: role of muscarinic antagonism in antipsychotic-induced diabetes and hyperglycemia.

Treatment with the atypical antipsychotics olanzapine and clozapine has been associated with an increased risk for deterioration of glucose homeostasis, leading to hyperglycemia, ketoacidosis, and diabetes, in some cases independent of weight gain. Because these events may be a consequence of their ability to directly alter insulin secretion from pancreatic beta-cells, we determined the effects of several antipsychotics on cholinergic- and glucose-stimulated insulin secretion from isolated rat islets. At concentrations encompassing therapeutically relevant levels, olanzapine and clozapine reduced insulin secretion stimulated by 10 micromol/l carbachol plus 7 mmol/l glucose.

Prostaglandin E2 receptor subtype EP-2 is not involved in the induction of non-pregnant guinea pig uterine contractions associated with terminal pregnancy.

Prostaglandin E2 (PGE2) exerts its biological effects through 4 different receptor subtypes, EP-1, EP-2, EP-3, and EP-4. Recently we have demonstrated the importance of the prostaglandin E2 receptor subtype EP-2 in the healing of bone defects and fractures. This discovery led to the identification of CP-533,536, an EP-2 selective agonist, a promising therapeutic alternative for the enhancement of bone healing and the treatment of fractures (J Bone Miner Res 18 (2003) 2033).

Cardiovascular effects of CP-96,345, a non-peptide blocker of tachykinin NK1 receptors.

CP-96,345, a non-peptide, selective tachykinin NK1 receptor blocker and its inactive enantiomer, CP-96,344, inhibit ligand binding of phenylalkylamine but not dihydropyridine Ca2+ channel antagonists. Whether these Ca2+ channel antagonist properties of CP-96,345 and CP-96,344 can be expressed as cardiovascular effects in vitro and in vivo is unknown. The cardiovascular effects of CP-96,345 and CP-96,344 in isolated vascular smooth muscle and in anesthetized dogs were compared to those of verapamil and nifedipine, phenylalkylamine and dihydropyridine Ca2+ channel antagonists, respectively.

Inhibition of tachykinin-induced hypotension in dogs by CP-96,345, a selective blocker of NK-1 receptors.

The effects of substance P, neurokinin A, neurokinin B, [Sar9, Met(O2)11]-substance P, [Nle10]-neurokinin A (4-10) and senktide (succinyl-[Asp6, MePhe8]-substance P (6-11)) on blood pressure and heart rate were studied in anesthetized dogs. Dose-dependent decreases in blood pressure and increases in heart rate were caused by each peptide except senktide. The latter elicited weak hypotensive or hypertensive responses at high doses.