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Biomedical subjects

C J Lynch

Publications and source records attributed to C J Lynch.

At least 19 recordsLinked to original sources
PubMed1992

Pyruvate carboxylase in genetic obesity.

Immunoblotting and protein microsequencing were used to identify several adipocyte proteins expressed in an obesity-related fashion in the Zucker rat. One of these was a 116-kDa particulate protein (p116). The p116 levels in adipocytes from 5- to 7-wk-old obese Zucker rats were two- to fivefold higher on a per milligram of protein basis than levels in lean animals and decreased after the induction of streptozotocin-induced diabetes mellitus. This suggests the change may be related to the actions of insulin. Hepatic levels of p116 did not change. The p116 was purified to homogeneity from obese Zucker rat adipocytes, and polyclonal antisera were prepared against the purified protein in rabbits. Microanalysis of electroblotted p116 proteolytic fragments suggested that p116 was pyruvate carboxylase (PC). Other evidence that p116 was PC included the following: 1) p116 contained biotin, 2) p116 in particulate subcellular fractions was soluble after freeze-lysis, 3) antibodies to p116 reacted with purified hepatic PC, 4) p116 and purified hepatic PC had identical pI and relative molecular weight values, and 5) similar changes were detected in adipocyte p116 and PC enzyme activity during obesity and after the induction of streptozotocin-induced diabetes mellitus. Increased adipose tissue PC probably contributes to the increased lipogenic capacity of young obese Zucker rat adipocytes.

Amino Acid Sequence↗
PubMed1992

Anterior ankle dislocation with associated trigonal process fracture. A case report and literature review.

Anterior ankle dislocations without concomitant malleolar fractures are rare injuries. Review of the English-language literature disclosed only three previously reported cases. A 21-year-old man sustained an isolated anterior ankle dislocation with an associated fracture of the trigonal process, which was reduced without difficulty. At follow-up examination 33 months later, the patient's major complaint was chronic, posttraumatic peroneal tendon dislocation. The proposed mechanism of injury suggested in this case is forced plantar flexion.

Adult↗
PubMed1989

Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides.

Adenylate cyclase in liver plasma membranes from streptozotocin-diabetic (STZ) or BB/Wor spontaneously diabetic rats showed increased responsiveness to GTP, glucagon, fluoroaluminate, and cholera toxin. Basal or forskolin-stimulated activity was unchanged in STZ rats, but increased in BB/Wor rats. No change in the alpha-subunit of Gi (alpha i) was observed in STZ or BB/Wor rats using pertussis toxin-stimulated [32P]ADP-ribosylation. Immunodetection using antibodies against the COOH-terminal decapeptides of alpha T and alpha i-3 showed no change in alpha i in STZ rats and a slight decrease in BB/Wor rats. Angiotensin II inhibition of hepatic adenylate cyclase was not altered in either diabetic rat. In both models of diabetes, Gs alpha-subunits were increased as measured by cholera toxin-stimulated [32P]-ADP-ribosylation of 43-47.5-kD peptides, reconstitution with membranes from S49 cyc- cells or immunoreactivity using antibodies against the COOH-terminal decapeptide of alpha s. These data indicate that STZ-diabetes increases hepatic Gs but does not change Gi or adenylate cyclase catalytic activity. In contrast, BB/Wor rats show increased hepatic Gs and adenylate cyclase. These changes could explain the increase in hepatic cAMP and related dysfunctions observed in diabetes.

Adenosine Diphosphate Ribose↗
PubMed1988

Agonist-induced down-regulation of the angiotensin II receptor in primary cultures of rat hepatocytes.

The ability of angiotensin II to down-regulate its receptor was tested on rat hepatocytes in primary culture for 4 h. Angiotensin II treatment decreased [3H]angiotensin II specific binding in a concentration- and time-dependent manner. The effect was maximum with 1 microM angiotensin II and after 2 h. There was a decrease in the maximum number of binding sites (56% of control) with no significant effect on the apparent dissociation constant. The down-regulation was blocked by the angiotensin II antagonist [Val4,Ile7]angiotensin III and was not induced by other hormones (e.g. vasopressin, norepinephrine, or glucagon) or by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate or A23187 ionophore. The decrease in angiotensin II receptors resulted in correlated decreases in the potency of angiotensin II to activate phosphorylase or lower glucagon-induced cAMP accumulation. However, high concentrations of the agonist were still able to elicit maximal responses in both parameters. Down-regulation of the receptor was not dependent upon active Gi, since it was still observed after ADP-ribosylation and inactivation of Gi by pertussis toxin. The above results indicate that the down-regulation of the hepatic angiotensin II receptor induced by its agonist is homologous and does not involve Gi, Ca2+, or protein kinase C. The correlation of receptor loss with decreases in the potency of angiotensin to activate phosphorylase and inhibit glucagon-induced cAMP accumulation is consistent with the idea that a single receptor population regulates two different messengers, i.e. calcium and cAMP.

Angiotensin II↗
PubMed1988

Formation of the high-affinity agonist state of the alpha 1-adrenergic receptor at cold temperatures does not require a G-protein.

Two methods were employed to uncouple hepatic alpha 1-adrenergic receptors from their associated G-protein (termed Gp) in order to determine whether locking of the alpha 1-receptor in a high-affinity agonist state at cold temperatures (2 degrees C) represents formation of a ternary complex. Uncoupling is defined as the inability to observe the GppNHp-sensitive, high-affinity agonist state of the receptor in [3H]prazosin competition binding studies performed at 25 degrees C. The first method for achieving uncoupling involved brief alkalinization and resulted in greater than 95% loss of several G-proteins. The second method involved proteolytic cleavage of either part or all of the alpha 1-receptor coupling domain from the binding domain. Following either treatment, receptors were converted to the high-affinity agonist state at 2 degrees C. Thus, while formation of the high-affinity state of the receptor at higher temperatures may require Gp, formation of this state at 2 degrees C does not require Gp or even the entire alpha 1-adrenergic receptor.

Animals↗
PubMed1988

Role of guanine nucleotide regulatory proteins and inositol phosphates in the hormone induced mobilization of hepatocyte calcium.

Treatment of isolated hepatocytes with F- produced a concentration-dependent activation of phosphorylase, efflux of Ca2+, rise in [Ca2+]i, increase in Ins 1,4,5-P3 levels, decrease in PI-4,5-P2 levels, and increase in DAG levels. The levels of intracellular cAMP were decreased by NaF. The effects of NaF were potentiated by AlCl3. This potentiation was abolished by the Al3+ chelator deferoxamine. These results illustrate that AlF4- can mimic the effects of Ca2+-mobilizing hormones in hepatocytes and suggest that the coupling of the receptors for these hormones to the hydrolysis of PI-4,5-P2 is through a guanine nucleotide-binding regulatory protein. This is because AlF4- is known to modulate the activity of other guanine nucleotide regulatory proteins (Gi, Gs, and transducin). Calcium-sensitive inositide release in a purified rat liver plasma membrane preparation was increased by calcium-mobilizing hormones in the presence of guanine nucleotides. Vasopressin-stimulated inositide release was evident in the presence of GTP or GTP gamma S. The guanine nucleotide and hormonal stimulation was evident on both inositide production and PI 4,5-P2 degradation. Treatment of plasma membranes with cholera toxin or islet activating protein or prior injection of animals with islet activating protein did not affect stimulation of inositide release by GTP gamma S or GTP gamma S plus vasopressin. The results suggest that calcium-mobilizing hormones stimulate polyphosphoinositide breakdown in rat liver plasma membranes through a novel guanine nucleotide binding protein. The GTPase activity of rat liver plasma membranes was stimulated 20% by 10(-8) M vasopressin. The vasopressin-stimulated GTPase activity was not inhibited in plasma membranes that had been ADP-ribosylated with either cholera toxin or pertussis toxin. When membranes that had been solubilized after preincubation with [3H]vasopressin were subjected to sucrose gradient centrifugation, most of the protein-bound [3H]vasopressin migrated as a single band, also, there was a GTPase activity that migrated with the bound [3H]vasopressin. This peak of bound [3H]vasopressin was decreased 90% when the sucrose gradient centrifugation was run in the presence of 10 M GTP gamma S. Direct evidence that a GTP-binding protein was present in the [3H]vasopressin peak was obtained by the immuno-detection of a 35 kDa beta subunit of a GTP-binding protein and a 40 kDa alpha subunit. These results support the conclusion that liver plasma membranes contain a GTP-binding protein that can complex with the vasopressin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Calcium-mobilizing hormones and phorbol myristate acetate mediate heterologous desensitization of the hormone-sensitive hepatic Na+/K+ pump.

The Na+/K+ pump in rat hepatocytes is stimulated in response to Ca2+-mobilizing hormones such as [arginine]vasopressin (AVP), angiotensin II and adrenaline, as well as tumour promoters such as 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). The ability of these agents to increase cellular contents of diacylglycerol and activate protein kinase C may be necessary to observe this response. In the present work, ouabain-sensitive 86Rb+ uptake was studied in isolated rat hepatocytes to help to explain why stimulation of the Na+/K+ pump by Ca2+-mobilizing hormones and tumour promoters is not temporally sustained relative to other hormone responses. A transient stimulation (3-4 min) of the Na+/K+ pump was observed in hepatocytes exposed to high (10 nM), but not low (0.1 nM), concentrations of AVP. Experiments with the Ca2+ chelator EGTA and the Na+ ionophore monensin indicate that the rapid secondary decrease in Na+/K+-pump activity which occurs after AVP stimulation is not due to changes in cytosolic Ca2+ and Na+ concentrations. When added after the stimulation and rapid decrease in Na+/K+-pump activity induced in hepatocytes by a high concentration of AVP, a second challenge with AVP or PMA failed to stimulate the pump. Similarly, previous exposure of hepatocytes to angiotensin, adrenaline or PMA attenuated the subsequent Na+/K+-pump responses to AVP and PMA. In contrast, previous exposure to AVP had no significant effect on subsequent stimulation of the Na+/K+-pump by monensin, glucagon, forskolin or 8-p-chlorophenylthio cyclic AMP. In addition, exposure to monensin had no effect on subsequent responses to AVP and PMA. These data indicate that high concentrations of Ca2+-mobilizing hormones and PMA result in heterologous desensitization of the hepatic Na+/K+ pump to subsequent stimulation by Ca2+-mobilizing hormones and PMA, but not by cyclic-AMP-dependent agonists or monensin.

Angiotensin II↗
PubMed1987

The acoustic characteristics of the cry of an infant with unilateral vocal fold paralysis.

We have previously shown the acoustic similarity among well, full-term infants of the same post-conceptional and post-partum ages (Int. J. Pediat. Otorhinolaryngol., 10 (1985) 1-8). The objective of that research was to provide a template against which the cries of any given infant may be compared. This paper shows a more detailed analysis of both the normal infants' cries and the cry of an infant with a unilateral vocal fold paralysis. It is evident from this analysis that this infant's cry is not normal as it displays a spectrum not found in the cries of normal infants. What this research shows is that a technique is available with which it is possible to make a screening identification of those infants who merit further investigation. It is an objective of such research to determine if the cry of a given infant is abnormal in specifiable, and therefore diagnostic, ways. In this instance, we can conclude that the cry of this infant differs from that of one with a normal airway.

Crying↗
PubMed1987

Spontaneous cigarette brand switching: consequences for nicotine and carbon monoxide exposure.

A group of smokers who had participated in smoking-related studies three to six years earlier were re-studied to assess changes in their smoking practices. Individuals who smoked the same brands of cigarettes showed no change in plasma cotinine (reflecting exposure to nicotine) or expired carbon monoxide (CO) concentration. Those who switched to cigarettes of lower nicotine yield (average decrease 38 per cent) showed reduced plasma cotinine concentrations, due primarily to smoking fewer cigarettes per day. The intake of nicotine per cigarette was not different. Subjects who smoked cigarettes of higher yield (102 per cent increase) had higher cotinine and CO levels, due to greater intake per cigarette.

Adult↗
PubMed1986

The hormone-sensitive hepatic Na+-pump. Evidence for regulation by diacylglycerol and tumor promoters.

Ouabain-sensitive 86Rb+ uptake by isolated rat hepatocytes was studied to elucidate how Ca2+-mobilizing hormones stimulate the Na+-pump. Stimulation of this uptake was observed with concentrations of vasopressin ([8-arginine]vasopressin, AVP), angiotensin II, and norepinephrine which elicited Ca2+ mobilization and phosphorylase activation. These results suggested that changes in cytosolic Ca2+, mediated by inositol trisphosphate, might trigger sodium pump stimulation by AVP. However, in hepatocytes incubated in Ca2+-free Krebs-Henseleit buffer, Na+-pump activity was not altered over 15 min by either 1.5 mM EGTA or 1.5 mM Ca2+. Furthermore, incubation of cells in 5 mM EGTA for 15-30 min drastically impaired the ability of AVP to increase cytosolic Ca2+, but only modestly attenuated AVP-stimulated Na+-pump activity. Two tumor promoters, phorbol myristate acetate (PMA) and mezerein, stimulated Na+/K+-ATPase-mediated transport activity. Similarly, addition of synthetic diacylglycerols or of exogenous phospholipase C from Clostridium perfringens to increase endogenous diacylglycerol levels also resulted in a stimulation of the Na+-pump in the absence of changes in cytosolic or total cellular Ca2+ levels. Stimulation of the Na+-pump by the combination of maximal concentrations of PMA and AVP did not produce an additive response, and both agents displayed a transient time course, suggesting that the two agents share a common mechanism. Stimulation of the Na+-pump by AVP and PMA was not blocked by amiloride analogs which inhibit Na+/H+ exchange, but these compounds blocked the action of insulin. These data suggest that the elevated Na+/K+-ATPase-mediated transport activity observed in hepatocytes following exposure to Ca2+-mobilizing hormones is a consequence of stimulated diacylglycerol formation and may involve protein kinase C.

Angiotensin II↗
PubMed1986

Alpha-subunits of Ns are released from the plasma membrane following cholera toxin activation.

Cholera toxin (CT) and islet-activating protein (IAP, a Bordetella pertussis toxin) were employed to test the hypothesis that GTP-binding regulatory proteins are released from plasma membranes to a greater extent when 'activated' than when 'inactivated'. CT, which activates Ns (the stimulatory GTP-binding regulatory protein of the adenylate cyclase system), catalyzed the incorporation of radioactivity from [32P]NAD into 45 and 47.5 kDa peptides associated with rat liver plasma membranes. Following ADP-ribosylation and centrifugation at 100000 X g for 1 h, approx. 30-35% of these CT-labelled peptides were no longer associated with the plasma membranes, but were recovered from the supernatant fraction. IAP, which inactivates Ni (the inhibitory GTP-binding regulatory protein of the adenylate cyclase system) catalyzed the incorporation of radioactivity from [32P]NAD into a 41 kDa peptide associated with the membranes. However, in contrast to the CT-labelled peptides, typically less than 5% of the IAP-labelled peptide was found in the 100000 X g supernatant fraction, but rather was almost exclusively associated with the membrane pellet. The data indicate that the alpha-subunits of Ns are released from the plasma membrane following activation, and support the hypothesis that the beta gamma-subunits act to anchor the alpha-subunits to the plasma membrane.

Adenosine Diphosphate Ribose↗
PubMed1986

An endogenous Ca2+-sensitive proteinase converts the hepatic alpha 1-adrenergic receptor to guanine nucleotide-insensitive forms.

An iodoazido[125I]prazosin analogue was employed to photoaffinity label alpha 1-adrenergic receptors in rat liver plasma membranes. Labeled proteins were separated by gradient polyacrylamide gel electrophoresis in sodium dodecyl sulfate, and (-)-epinephrine displacement of [3H]prazosin binding was concurrently measured in the presence or absence of guanosine 5'-O-(gamma-thiotriphosphate) (GTP[gamma S]). Inclusion of EGTA and/or proteinase inhibitors during membrane preparation and incubation increased the effect of GTP[gamma S] on alpha 1-adrenergic agonist binding and this could be correlated with increased concentrations of a 78 kDa photoaffinity labeled protein. In contrast, omission of EGTA or addition of exogenous Ca2+ diminished or abolished the effect of GTP[gamma S] on binding and caused loss of the 78 kDa form and the appearance of lower molecular weight labeled proteins. Age-dependent differences in GTP[gamma S] effects on alpha 1-adrenergic agonist binding were abolished when membranes were prepared and incubated in the presence of EGTA and proteinase inhibitors. However, the 78 kDa photoaffinity labeled protein observed in adult rats (over 225 g body weight) was not apparent in membranes from younger rats (50-75 g), even when the membranes were prepared and incubated in the presence of EGTA and proteinase inhibitors. Instead, a 68 kDa species was the major labeled protein. These data suggest that GTP effects on alpha 1-adrenergic agonist binding in rat liver membranes require the presence of either a 68 or 78 kDa alpha 1-adrenergic binding protein. Failure to inhibit proteolysis in the membranes leads to the generation of lower-molecular-weight binding proteins and the loss of GTP effects on alpha 1-adrenergic agonist binding, although [3H]prazosin binding characteristics are not changed. It is suggested that either the proteolyzed forms of the alpha 1-adrenergic receptor are unable to couple to a putative guanine nucleotide-binding regulatory protein, or that such a protein is concurrently proteolyzed and is thus unable to couple to the receptor.

Adrenergic alpha-Antagonists↗
PubMed1986

Mouth versus deep airways absorption of nicotine in cigarette smokers.

Nicotine from the alkaline smoke of cigars is absorbed through the buccal mucosa, but such absorption from the more acidic smoke of American cigarettes has not been reported. Forty-one male and 52 female smokers were studied under normal ventilation and smoking conditions, and under high ventilation and controlled smoking conditions that restricted intake to the mouth only, with no inhalation. The major finding is that there is virtually no intake of nicotine through the buccal mucosa while smoking American cigarettes. Confirming prior reports, plasma nicotine and expired CO levels showed no correlation with the analytical yields of nicotine and CO of the cigarettes smoked. Fifteen nonsmokers (7 male, 8 female) participated in this study as controls. Data from these subjects provided additional information regarding absorption of nicotine and carbon monoxide during passive smoking. Within the highly ventilated environment, there was no significant change of CO and nicotine levels of nonsmokers. However, within the normally ventilated environment, there was minimal increase in both substances, statistically significant only for nicotine. These results suggest that nicotine may be a better indicator of exposure to second-hand smoke than carbon monoxide.

Absorption↗
PubMed1986

Decline of U.S. cancer mortality rates: expert estimates of past underreporting.

Regulatory and public health policies in the United States are predicated on the uncritical acceptance of an alleged explosion in cancer mortality rates. In reality, several studies offer evidence that cancer mortality went underreported as one goes back in time, due to progressive deficiencies in diagnostic and registration practices. Because the absence of historical records precludes a comprehensive direct verification, a group of experts were polled to estimate the impact of this bias on U.S. cancer mortality statistics. The nature of this exercise speaks against a numerical interpretation of the results; however, their broad analogic meaning suggests that age-adjusted mortality and probably the incidence of leading cancers have significantly declined for decades, with the major exception of respiratory tract cancers.

Biometry↗
PubMed1986

Differences in the role of Na+/K+-ATPase during alpha 1-adrenergic events in rat and rabbit aorta.

Transport activity of the Na+/K+-ATPase was studied in rat and rabbit aorta under basal and agonist-stimulated conditions. Basal ouabain-sensitive 86Rb+ uptake was 2.9-fold higher in rat tissues as compared to rabbit tissues. This higher uptake in the rat was associated with a greater sensitivity to the Na+/H+ exchange inhibitor amiloride. Stimulation of alpha 1-adrenergic receptors by norepinephrine (NE) or phenylephrine (PE) resulted in an increase in ouabain-sensitive 86Rb+ uptake, whose temporal pattern differed between arteries of the two species. In rat aorta the increase was maximal during the first 2 min of agonist exposure reaching approximately a 50% higher rate of uptake than controls while rabbit aorta exhibited a steady rise in 86Rb+ uptake. Removal of extracellular Ca2+ by EGTA (1 mM) for 10 min resulted in an activation of Na+/K+-ATPase-related 86Rb+ uptake after which PE was still capable of causing a further increase, suggesting that Ca2+ influx is not responsible for the receptor-induced stimulation. Removal of extracellular Na+ reduced the PE-induced stimulation, while amiloride did not block the agonist effect. To characterize the role of the Na+/K+-ATPase during contractile events, receptor-induced 45Ca2+ uptake, 45Ca2+ release and contraction were compared in rat and rabbit aorta following Na+/K+-ATPase inhibition. Rat responses to PE were readily inhibited by ouabain or K+-free conditions, while rabbit responses were relatively resistant. 45Ca2+ extrusion and relaxation following alpha 1-adrenergic receptor stimulation were both highly dependent on activity of the Na+/K+-ATPase in rat aorta. These species' differences in Na+/K+-ATPase transport activity and its role in the regulation of contractility illustrate an example of heterogeneity in the ionic control of arterial tone.

Animals↗
PubMed1986

Effect of islet-activating pertussis toxin on the binding characteristics of Ca2+-mobilizing hormones and on agonist activation of phosphorylase in hepatocytes.

Islet-activating protein (IAP, a Bordetella pertussis toxin) was employed to test the hypothesis that the inhibitory GTP-binding regulatory protein of adenylate cyclase (Ni) mediates GTP effects on the binding of Ca2+-mobilizing hormones to liver plasma membranes and is involved in calcium mobilization stimulated by these agonists. IAP added to normal liver plasma membranes catalyzed the incorporation of radioactivity from [32P]NAD into a 41,000-Da peptide (presumably the alpha-subunit of Ni). However, no such incorporation was observed in liver membranes prepared from rats 24 hr after intraperitoneal injection of IAP. Angiotensin II attenuated glucagon-stimulated increases in cAMP in hepatocytes prepared from control but not IAP-treated rats. In contrast, following IAP treatment, no changes were observed in the ability of glucagon, vasopressin, angiotensin II, or epinephrine to activate phosphorylase; nor did this treatment alter [3H]vasopressin binding or epinephrine displacement of [3H]prazosin binding. However, IAP treatment decreased [3H]angiotensin II binding affinity when studies were performed in the absence but not the presence of 5'-guanylylimidodiphosphate (GppNHp). This shift was small and represented only 5-8% of the shift in apparent Kd elicited by GppNHp in untreated membranes. In vitro studies with IAP confirmed the results of the radioligand binding studies using in vivo IAP treatment. The effects of NaCl on [3H]angiotensin II binding were also tested but were not typical of other receptors which couple to Ni. The data suggest that, although a small population of hepatic angiotensin II receptors couple to Ni and attenuate glucagon-stimulated increases in cAMP, vasopressin, alpha 1-adrenergic, and the majority of angiotensin II receptors do not interact significantly with Ni. Thus, although there is evidence that agonist-induced Ca2+ mobilization requires a GTP-binding regulatory protein, this protein does not appear to be Ni in rat liver.

Adenylate Cyclase Toxin↗
PubMed1985

Inhibition of hepatic alpha 1-adrenergic effects and binding by phorbol myristate acetate.

Treatment of isolated hepatocytes with the tumor-promoting agent, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) produced a time- and dose-dependent, non-competitive inhibition of alpha 1-adrenergic responses, including the activation of phosphorylase, increase in Ca2+ efflux, increase in free cytosolic Ca2+, and release of myo-inositol-1,4,5-P3. The actions of [8-arginine] vasopressin (AVP) on liver cells were also inhibited by PMA, but the inhibition could be overcome by high AVP concentrations. No significant inhibition of beta-adrenergic and glucagon-mediated activation of phosphorylase was induced by PMA and no inhibitory or synergistic effects of PMA were observed on the dose-dependent activation of phosphorylase by the Ca2+ ionophore A23187. In radioligand binding studies, PMA did not directly interfere with [3H]prazosin specific binding, the displacement of [3H]prazosin by (-)-norepinephrine nor with [3H]AVP specific binding to purified liver plasma membranes. Plasma membranes prepared from livers perfused with PMA exhibited a 30-44% reduction in [3H]prazosin binding capacity. Under identical conditions [3H]AVP binding was unchanged. The alpha 1-receptors remaining in membranes from PMA-treated livers had equivalent affinities for [3H]prazosin and (-)-norepinephrine, and were unaffected in terms of coupling to guanine nucleotide-regulating proteins as indicated by the ability of guanosine 5'-(beta, gamma-imido)triphosphate to promote the conversion of the remaining alpha 1-receptors into a low affinity state. These data indicate that tumor promoters are potent antagonists of alpha 1-adrenergic and vasopressin (low dose) responses in liver. It is proposed that PMA acting via protein kinase C (which presumably mediates the action of PMA) exerts its inhibitory action on alpha 1-adrenergic responses at the alpha 1-adrenergic receptor itself and also at a site close to or before myo-inositol-1,4,5-P3 release.

Animals↗