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R Villalobos-Molina

Publications and source records attributed to R Villalobos-Molina.

At least 55 records · Page 3Linked to original sources
PubMed1994

Reductions of 56Fe heavy-particle irradiation-induced deficits in striatal muscarinic receptor sensitivity by selective cross-activation/inhibition of second-messenger systems.

Recent experiments have revealed radiation-induced (600 MeV/u 56Fe energetic particles) losses of sensitivity of rodent neostriatal muscarinic receptors to stimulation by cholinergic agonists that appears as reductions in oxotremorine enhancement of K(+)-evoked dopamine release. These losses were postulated to be the result of radiation-induced alterations early in phosphoinositide-mediated signal transduction. Additional findings indicated that if the ligand-receptor-G protein interface was by passed no radiation deficits were seen. In the present study, radiation-induced deficits in K(+)-evoked dopamine release were examined in perifused striatal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe particles (600 MeV/u). Results showed that these deficits could be reduced by co-applying combinations of various pharmacological agents that were known to have differential effects on various second messengers such as 1,4,5-inositol-trisphosphate (IP3). Combinations included oxotremorine-carbachol, and either oxotremorine or carbachol with arginine vasopressin or arachidonic acid. These results are discussed in terms of putative radiation-induced changes in receptor-containing membranes which alter receptor-G protein coupling/uncoupling.

Analysis of Variance↗
PubMed1993

Pharmacological evidence for interactions between 5-HT1A receptor agonists and subtypes of alpha 1-adrenoceptors on rabbit aorta.

This study was designed to determine if alpha 1-adrenoceptors are involved in the vascular responses to 5-HT1A receptor agonists. Buspirone (3.1 x 10(-7)-3.1 x 10(-5) M) and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT; 3.1 x 10(-6)-10(-4) M) elicited contractions of rabbit aorta rings which were blocked by prazosin (10(-9)-5.6 x 10(-9) M), but which were unaffected by reserpine pretreatment (1 mg/kg i.p.). 5-Methylurapidil (10(-7) and 10(-6) M) blocked contractions elicited by 8-OH-DPAT and by buspirone, whereas chloroethylchonidine (10(-5) and 10(-4) M) inhibited only the effect of buspirone. In addition, these 5-HT1A receptor agonists relaxed arteries precontracted with alpha-adrenoceptor agonists in a similar range of concentrations in which they elicited contraction. Moreover, 8-OH-DPAT and buspirone protected the alpha-adrenoceptors from the irreversible blockade provoked by phenoxybenzamine (10(-7) M), as judged by the norepinephrine contraction and stimulated phosphatidylinositol labeling. According to these results the contractile and relaxant effects elicited by 5-HT1A receptor agonists are a consequence of a direct interaction with alpha 1-adrenoceptors. The contraction elicited by 8-OH-DPAT may be mediated by alpha 1A-adrenoceptors, whereas both alpha 1A- and alpha 1B-adrenoceptors may mediate the effect of buspirone in rabbit aorta.

Adrenergic alpha-Agonists↗
PubMed1993

Vascular effects of ipsapirone are related with subtypes of alpha 1-adrenergic receptors.

The aim of this study was to provide further evidence about the participation of alpha 1-adrenoceptors in the vascular responses elicited by ipsapirone. This 5-HT1A agonist displayed vasodilator activity only when aortic rings were precontracted by alpha-adrenergic compounds. The relaxant effect was particularly evident when rings were precontracted with methoxamine (selective alpha 1A-adrenergic agonist). On the other hand, ipsapirone but not chloroethylclonidine (selective alpha 1B-adrenergic antagonist), clearly displaced norepinephrine and methoxamine vasocontractile concentration-response curves to the right. Finally, ipsapirone protected the alpha-adrenoceptors form the irreversible blockade provoked by phenoxybenzamine, as judged by the norepinephrine contraction and stimulated phosphatidylinositil labeling. Accordingly the relaxant effect elicited by ipsapirone in aortic rings precontracted with alpha-adrenergic agonists and the protective action against blockade by phenoxybenzamine shown by this agent are proof of its ability to occupy alpha 1-adrenoceptors. Specifically, alpha 1A-adrenergic receptors seem to be involved in ipsapirone vascular effects, since this agent selectively relaxed aortic preparation precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited the contractile effect of this agonist. In summary, the present findings can be explained by accepting that ipsapirone may act as an antagonist at alpha 1A-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1992

Alpha 1-adrenergic stimulation of low Km GTPase in rat striata is diminished with age.

The effect of norepinephrine and epinephrine on the activity of low Km GTPase was studied in striata from young and old rats. Results showed that the amines stimulated the low Km GTPase activity of both young and old animals in a concentration-dependent manner. There was no differential effect of the amines as a function of age, but the stimulated low Km GTPase activity was significantly lower in the aged tissue.

Aging↗
PubMed1992

Alpha 1-adrenoceptors in parotid cells: age does not alter the ratio of alpha 1A and alpha 1B subtypes.

Epinephrine stimulation of 45Ca2+ efflux and inositol 1,4,5-trisphosphate ((1,4,5)IP3) production in parotid cell aggregates from mature rats was greatly inhibited (approximately 70%) by WB 4101 and 5-methylurapidil as compared to a small decrease by chloroethylclonidine (approximately 30%). The combination of WB 4101 or 5-methylurapidil and chloroethylclonidine completely blocked the action of epinephrine. The same relative inhibition was observed with senescent animals. The results suggest (1) that rat parotids contain both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, in an approximate functional ratio of 70:30, (2) that this relative ratio is not altered during aging, and (3) that both receptors partially mediate 45Ca2+ efflux and (1,4,5)IP3 production in this system.

Adrenergic alpha-Antagonists↗
PubMed1992

Altered coupling of alpha 1-adrenergic receptor-G protein in rat parotid during aging.

A possible role for altered signal transduction mechanisms in impaired alpha 1-adrenergic-stimulated secretory function during aging was investigated in parotid cells prepared from adult (6 mo) and old (24 mo) rats. Compared with adults, epinephrine-stimulated 45Ca2+ efflux and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production were reduced 31 and 36% in cells of old rats, respectively. There was a highly significant correlation between 45Ca2+ efflux and Ins(1,4,5)P3 production. In saponin-permeabilized cells, no significant differences in Ins(1,4,5)P3-stimulated 45Ca2+ efflux in adult and old preparations were observed. When G proteins were stimulated by guanosine 5'-O-(3-thiotriphosphate) or NaF, no age differences in Ins(1,4,5)P3 production were detected. Stimulation of phosphoinositide-specific phospholipase C (PLC) by CaCl2 in adult and old cells was also comparable. Moreover, no differences in immunolabeled common alpha (GTP binding site), Gi alpha, PLC-gamma, or PLC-delta could be detected in either cytosol or membranes of adult and old preparations. In the absence of 5'-guanylylimidodiphosphate [Gpp(NH)p], no age-related changes in epinephrine competition for [3H]prazosin binding sites were observed. Approximately 30% of the agonist binding sites existed in a high-affinity form at both ages. Gpp(NH)p caused large rightward shifts of epinephrine displacement curves in adult membranes (converting all binding sites to the low-affinity form), but not old. Moreover, epinephrine was much more effective in stimulating G protein low-Km GTPase in parotid membranes from adult than old rats. These data suggest that age-related impairments in alpha 1-adrenergic responsiveness are mediated, at least in part, by the functional alterations in the coupling of G proteins with alpha 1-adrenergic receptors.

Aging↗
PubMed1991

Alpha 1-adrenoceptor subtypes in aorta (alpha 1A) and liver (alpha 1B).

The effect of several alpha 1 adrenoceptor antagonists on the alpha 1-adrenoceptor-mediated stimulation of phosphatidylinositol labeling was studied comparatively in rat hepatocytes and rabbit aorta. It was observed that 5-methyl urapidil and WB 4101 were much more potent in rabbit aorta than in hepatocytes. The orders of potency were prazosin much greater than 5-methyl urapidil greater than or equal to WB 4101 in liver cells and WB 4101 greater than or equal to 5 methyl urapidil = prazosin in aorta. Treatment with chlorethylclonidine inhibited 70-80% of the stimulation of labeling induced by epinephrine in rat liver, but only 30-40% of that in aorta. Our data suggest the existence of two pharmacologically distinct receptors in these tissues i.e.m alpha 1A-adrenoceptors in aorta and alpha 1B in liver cells.

Adrenergic alpha-Antagonists↗
PubMed1990

Contrasting effects of phorbol dibutyrate and phorbol myristate acetate in rabbit aorta.

In rat hepatocytes, active phorbol esters inhibited the alpha 1-adrenergic stimulation of phosphatidylinositol labeling with the expected potency order: phorbol myristate acetate (PMA) greater than phorbol dibutyrate (PDB). In contrast, in rabbit aorta the alpha 1-adrenergic action was inhibited dose-dependently by PDB but not by PMA. Similarly PDB (but not PMA) induced a strong contraction in rabbit aorta. The phorbol ester-induced contraction developed slowly, was dose-dependent and independent of extracellular calcium. These effects of PDB in rabbit aorta were neither inhibited by the protein kinase inhibitor H-7 nor mimicked by the synthetic diacylglycerol, OAG. Our results raise some doubts on the mechanism(s) through which the actions of PDB take place in rabbit aorta.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Ca2+ ionophoretic activity of oligomers of prostaglandin B1 with isolated hepatocytes.

Chemically synthesized oligomers (dimers, trimers and tetramers) of 15-dehydroprostaglandin B1 and 16,16'dimethyl-15-dehydroprostaglandin B1 (16,16'diMePGB1) are effective Ca2+ ionophores with isolated mitochondria and in artificial systems. The trimer of 16, 16'diMePGB1 mediated a dose dependent Ca2+ efflux from intact rat hepatocytes; at 9.2 microM oligomer, Ca2+ was released primarily from the mitochondrial pool but at higher concentrations from other cellular pools. The 16, 16'diMePGB1 trimer did not alter Ca2+ release mediated by epinephrine suggesting that the PGB1 oligomer interacts at a different site. The oligomer also caused an activation of phosphorylase similar to that mediated by epinephrine.

Animals↗
PubMed1987

Accumulation of D-arginine by rat liver mitochondria.

The permeability of the inner mitochondrial membrane from rat liver to D-arginine was studied. By using safranin as a probe of the membrane potential, depolarization of energized liver mitochondria occurred in a dose-dependent fashion starting at 3.3 mmol/L of D- or DL-arginine. When ethidium bromide fluorescence was employed, a decrease in the membrane potential due to D- or DL-arginine was observed. A parallel significant change in succinate-induced respiration in rat liver mitochondria was found in response to osmotic swelling in 125 mmol/L of D-arginine salts. L-Arginine, L-glutamine, L-asparagine, L-ornithine, D-ornithine, and L-lysine did not modify the membrane potential at the concentrations tested. D-Arginine was not transformed into citrulline, but 1.0 mmol/L of the D-amino acid inhibited, by 42%, the state 3 of mitochondrial respiration using succinate as substrate. When D-arginine was used in combination with nigericin, a 40% inhibition of mitochondrial respiration in state 3 was recorded with succinate and with glutamate-malate as substrates.

Amino Acids↗
PubMed1985

Differential effects of adrenergic agonists and phorbol esters on the alpha 1-adrenoceptors of hepatocytes and aorta.

Epinephrine, norepinephrine and phenylephrine stimulate phosphatidylinositol labeling with [32P]Pi in both rat hepatocytes and rabbit aorta. Methoxamine was a full agonist for this effect in rabbit aorta whereas cirazoline and oxymetazoline were partial agonists. In contrast, these three agents (methoxamine, cirazoline and oxymetazoline) were unable to stimulate phosphatidylinositol labeling in rat hepatocytes. Furthermore, cirazoline and oxymetazoline were able to displace the dose-response curve to epinephrine in rat hepatocytes, i.e., they behaved as antagonists. Binding competition curves of these agents with labeled adrenergic ligands indicate that the affinity of alpha 1-adrenergic receptors in these two tissues (aorta and liver) for the different agents tested was very similar. In addition it was observed that phorbol myristate-acetate inhibited in a dose-dependent fashion the epinephrine-mediated stimulation of phosphatidylinositol labeling in hepatocytes but was without effect on the action of the amine in aorta. Our data suggest that stereochemical differences for alpha 1-adrenergic activation in liver and aorta may exist and indicate that the ability of phorbol esters to inhibit alpha 1-adrenergic effects is not universal.

Adrenergic alpha-Agonists↗
PubMed1983

Roles of alpha 1- and beta-adrenergic receptors in adrenergic responsiveness of liver cells formed after partial hepatectomy.

The adrenergic receptor involved in the action of epinephrine changed dramatically during the process of active proliferation which follows partial hepatectomy. In control or sham-operated animals, the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by epinephrine was mediated through alpha 1-adrenergic receptors. In contrast, in hepatocytes obtained from animals partially hepatectomized 3 days before experimentation, the receptor involved in the stimulation of these metabolic pathways by epinephrine was of the beta-adrenergic type. Interestingly, the adrenergic receptor involved in the metabolic actions of epinephrine, in hepatocytes from rats partially hepatectomized 7 days before experimentation was again of the alpha 1-subtype. Thus, it appears that during the process of liver regeneration which follows partial hepatectomy there is a transition in the type of adrenergic receptor involved in the hepatic actions of catecholamines from beta in the initial stages to later alpha 1. A similar transition seems to occur as the animal ages. Cyclic AMP accumulation in response to beta-adrenergic stimulation was significantly enhanced in hepatocytes obtained from rats partially hepatectomized 3 days before the experiment, as compared to control hepatocytes or cells obtained from animals operated 7 days before experimentation. This enhanced beta-adrenergic sensitivity is probably related to the increased number of beta-adrenergic receptors observed at this stage. However, a clear dissociation between cyclic AMP levels and metabolic effects was evidenced when the different conditions were compared. The number and affinity (for epinephrine or prazosin) of alpha 1-adrenergic receptors did not change at any stage of the process, which indicates that the markedly diminished alpha 1-adrenergic sensitivity observed in hepatocytes obtained from rats partially hepatectomized 3 days before experimentation is probably due to defective generation or intracellular processing of the alpha 1-adrenergic signal, rather than to changes at the receptor level.

Animals↗
PubMed1983

Sensitivity of liver cells formed after partial hepatectomy to glucagon, vasopressin and angiotensin II.

During the active proliferation which follows partial hepatectomy, the sensitivity of liver cells to glucagon is markedly diminished. In hepatocytes obtained from rats partially hepatectomized 3 days before experiments were performed, the dose-response curves to glucagon were shifted to the right by about two orders of magnitude as compared to those of the control cells. Later on (7 days after surgery) the dose-response to glucagon was still shifted to the right but by only one order of magnitude. These data are consistent with the diminution in the number of glucagon receptors in liver plasma membrane during liver regeneration reported by other authors. No stimulation of glycogenolysis, gluconeogenesis or ureogenesis was produced by vasopressin or angiotensin II in hepatocytes from rats partially hepatectomized 3 days before experimentation. However, phosphatidylinositol labeling was stimulated in these cells to a similar extent as in the controls. The ionophore A23187 was also ineffective in stimulating glycogenolysis in these cells. Later, 7 days after surgery, the hepatic responsiveness to vasopressin and angiotensin II was restored. The data suggest that, during the initial stages of liver regeneration, the enzymatic machinery of the hepatocyte is not sensitive to calcium-signalling.

Angiotensin II↗
PubMed1983

H1-histaminergic activation stimulates phosphatidylinositol labeling in rabbit aorta.

Histamine and 2-(2-aminoethyl)-thiazole induced dose-dependent increases in the labeling of phosphatidylinositol in rabbit aorta whereas impromidine was without effect. The effect of histamine was inhibited by antihistamines with the following order of potency: mepyramine greater than or equal to pyrilamine much greater than cimetidine. The data indicate that H1-histaminergic activation stimulates phosphatidylinositol labeling in rabbit aorta and suggest the involvement of a calcium-signaling process in the action of H1-histaminergic receptors.

Animals↗
PubMed1983

Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects.

Trifluoperazine and chlorpromazine inhibited in a dose-dependent manner the stimulation of glycogenolysis, gluconeogenesis, and ureogenesis due to alpha 1-adrenergic stimulation in rat hepatocytes. In contrast, the antipsychotic agents were unable to block the inhibition of adenylate cyclase due to alpha 2-adrenergic activation in hamster adipocytes. Binding experiments showed that trifluoperazine and chlorpromazine at low concentrations displaced tritiated dihydroergocryptine binding from rat liver membranes (alpha 1-adrenergic sites), whereas very large concentrations of the phenothiazine derivatives were required to displace dihydroergocryptine from hamster adipocyte membranes (alpha 2-adrenergic sites). It is concluded that chlorpromazine and trifluoperazine are much more potent at alpha 1- than at alpha 2-adrenergic receptors. The use of rat hepatocytes and hamster adipocytes to study the alpha-adrenergic subtype selectivity of drugs is proposed.

Adipose Tissue↗
PubMed1982

Cycloheximide: an adrenergic agent.

Cycloheximide, a widely used inhibitor of protein synthesis, stimulates glycogenolysis, gluconeogenesis and ureogenesis in isolated rat hepatocytes. The effects of cycloheximide were compared to those of norepinephrine. Both agents, cycloheximide and norepinephrine, produced slight increases in the levels of cyclic AMP (30% increases) which were blocked by propranolol. Interestingly, it was found that the metabolic actions of norepinephrine and cycloheximide (stimulation of glycogenolysis, gluconeogenesis and ureogenesis) were only slightly diminished by the beta adrenergic antagonist propranolol but abolished by the selective alpha 1 adrenergic antagonist prazosin. The ability of cycloheximide to inhibit protein synthesis was not affected by either prazosin or propranolol. It is concluded that the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by cycloheximide in rat hepatocytes, is an effect of the antibiotic independent of its ability to inhibit protein synthesis and that is mediated through activation of alpha 1 adrenoceptors. The adrenergic activity of cycloheximide should be considered when this drug is used as an inhibitor of protein synthesis.

Animals↗
PubMed1982

Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation.

Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with [32P]Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-[5,4-d] azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta.

Adrenergic alpha-Agonists↗