INTRODUCTION DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan) with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine). In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. METHODS The functional inhibitory characteristics of DHPEE were studi...

[3H]Nitrendipine binding to drug receptor sites associated with calcium channels is allosterically regulated by a diverse group of calcium channel antagonists. Verapamil, D-600 (methoxyverapamil), tiapamil, lidoflazine, flunarizine, cinnarizine, and prenylamine all reduce [3H]nitrendipine binding affinity. By contrast, diltiazem, a benzothiazepine calcium channel antagonist, enhances [3H]nitren...

alpha7 Nicotinic receptors are calcium permeant and provide neuroprotection against many insults. We investigated the roles of intracellular calcium ions and downstream calcium channels in this protection. The alpha7 agonist GTS-21 prevented pheochromocytoma cell death induced by nerve growth factor + serum deprivation over a 3-day interval. This effect was blocked by the intracellular calcium ...

The calcium channel gamma(6) subunit modulates low voltage-activated (LVA) calcium current in both human embryonic kidney (HEK) cells and cardiomyocytes, although the mechanism of modulation is unknown. We recently showed that gamma(6) contains a critical GxxxA motif in the first transmembrane domain (TM1) that is essential for its inhibition of the Cav3.1 (LVA) calcium current. In this study, ...

The renin-angiotensin-aldosterone (RAA) system is markedly activated in pregnancy. We evaluated if mineralocorticoid receptors (MR), a major component of the RAA system, are involved in the reduced vascular reactivity associated with pregnancy. Canrenoate (MR antagonist; 20 mg·kg(-1)·day(-1)) was administered to nonpregnant (NP) rats for 7 days and to pregnant rats from day 15 to 22 of gestatio...

Synaptic transmission between embryonic chick dorsal root ganglion (DRG) neurons and spinal cord neurons was studied in dissociated cell culture. Stimulation of DRG neurons evoked monosynaptic and polysynaptic excitatory responses in the spinal neurons. These responses could be reversibly blocked by application of 6-cyano-7-nitroquinoxaline-2,3-dione (a selective non-NMDA receptor antagonist) a...

To assess the influence of calcium channel antagonists on the expression of behavioral sensitization to cocaine, the L-type calcium channel antagonist diltiazem or the N-type calcium channel antagonist omega-conotoxin GVIA was microinjected into the medial nucleus accumbens before a systemic cocaine challenge injection among rats that were previously treated with daily systemic saline or cocain...

Regulation of calcium flux has been suggested to play a role in acute and chronic effects of opioids. Previous studies have shown calcium channel blockers can inhibit opioid agonist-induced downregulation of mu-opioid receptors and may reduce the magnitude of tolerance. In the present study, we determined if calcium channel blockade would affect increases in opioid receptor density and function...

We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30-40 days) and newborn (3-6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potential...

Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved in kidney function. It was hypothesized that human renal vascular excitation-contraction coupling involve...