Ca2+-channel agonists

In contrast, a low dose of the Ca2+ channel agonist BAY K 8644, a dihydropyridine derivative, antagonizes the antinociceptive effect of p-opioids. This is in agreement with results from Smith and Stevens (1995), who reported that Ca2+, when administered i.c.v., antagonizes morphine-induced antinociception in the mouse tail flick assay. The dose - response curve of morphine is shifted to the right by i.c.v. administration of calcium ions. 

Ca2+ channels, agonists produce transient increases in intracellular Ca2+ levels that probably result from the activation of the phosphoinositide hydrolysis and Ca2+ mobilization from intracellular stores (Kazmi et al., 2000). 

A large number of diugs interfere with the smooth muscle contraction. These compounds lower blood pressure and are referred to as antihypertensive. In this section, only those coumpounds will be mentioned that have a direct effect on smooth muscle tone. Phenylephrine is an agonist on most smooth muscles and activates ax adrenoceptors. Carbachol is an agonist on some smooth muscles and activates contraction through muscarinic receptors. Blockers of the ax-adrenoceptors such as prazosin and urapidil are competitive inhibitors of the ax-receptor in vascular and bladder smooth muscle. Phenoxybenzamine is an ineversible blocker of ax receptors and phentol-amine blocks ax and a2 receptors. Ca2+ channel blockers such as the dihydropyiidines, phenylalkyla-mines and benzothiazepines lower smooth muscle tone by blocking the L-type calcium channel. 

P2Y receptors are activated by adenine and uridine nucleotides. Most of the known P2Y receptors have been detected in the nervous system [21]. The majority of P2Y receptors inhibit neuronal N-type Ca2+ channels and M-type K+ channels. P2Y1 receptors are found exclusively on platelets, on their precursor megakaryocyte cells and on certain other cultured hematopoietic cells, such as K562 leukemia cells. They can be distinguished from other P2 receptors in that ADP is the most potent natural agonist and ATP is a competitive antagonist. ADP acts via a G protein to inhibit cyclic AMP accumulation, mobilize intracellular Ca2+ and stimulate granule secretion. ADP... 

These are (3-adrenergic agonists that act by stimulation of the enzyme, adenylyl cyclase, thereby increasing intracellular cAMP. This indirectly increases intracellular calcium, by induction of the active form of protein kinase followed by an influx of Ca2+ through open voltage-dependent Ca2+ channels (Figure 8.4). 

Potent anti nociception and reduced side-effects through the combination of p-opioid agonists with L-type Ca2+ channel antagonists... 

Garaulet, J.V., Laorden, M.L., Milanes, M.V. Effect of chronic administration of dihydropyridine Ca2+ channel ligands on sufentanil-induced tolerance to p- and K-opioid agonists in the guinea pig ileum myenteric plexus, Regulatory Peptides 1996, 63, 1-8. 

Holopainen I., Enkvist M. O. K., and Akerman K. E. O. (1989). Glutamate receptor agonists increase intracellular Ca2+ independently of voltage-gated Ca2+ channels in rat cerebellar granule cells. Neurosci. Lett. 98 57-62. 

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