Vasodilator effects on canine basilar artery induced by intracisternal interleukin-1 beta

The effect of interleukin-1 beta (IL-1 beta) on a cerebral artery was investigated in anesthetized dogs. Intracisternal administration of IL-1 beta (0.03 and 0.3 micrograms) dilated the canine basilar artery in a dose-dependent manner, without affecting systemic blood pressure or heart rate. The increase in diameter induced by 0.3 micrograms of IL-1 beta was 28.4% +/- 13.4% of control at 2 hours and was inhibited by 30 micrograms of the IL-1 beta receptor antagonist, zinc protoporphyrin (4.5% +/- 13.5%, P < 0.05). Interleukin-1 beta did not affect the concentration of nitric oxide metabolites in CSF. However, there was an increase in the concentration of eicosanoids in CSF, and the elevation of 6-keto-PGF1 alpha paralleled the vasodilation. Pretreatment with 30 micrograms of the selective inducible cyclooxygenase (COX-2) inhibitor NS-398 also inhibited the IL-1 beta-induced vasodilation significantly (5.9% +/- 9.4% at 2 hours, P < 0.01). Western blot analysis revealed the expression of a 68-kD COX-2-like protein in basilar artery extracts. These findings suggest that the IL-1 beta-induced vasodilator effect is linked to the prostaglandin cascade, predominantly to prostaglandin I2, by induction of COX-2, but not to the stimulation of nitric oxide metabolism.     

Giant fusiform basilar artery aneurysm: endovascular treatment by flow reversal in the basilar artery

We report a patient presenting with subarachnoid haemorrhage due to rupture of a giant fusiform aneurysm of the proximal basilar artery. The aneurysm was successfully treated by reversing blood flow in the basilar artery by balloon occlusions of both vertebral arteries proximal to the posterior inferior cerebellar artery origins. Substantial thrombosis and regression of the aneurysm was evident 4 months later.     

Spontaneous thrombosis of a basilar artery traumatic aneurysm in a child

Traumatic aneurysms are rare and occur most commonly in young adults; however, the relative frequency in the pediatric population is high, owing to the low prevalence of congenital saccular aneurysms in children. Traumatic aneurysms typically involve the anterior circulation, and spontaneous thrombosis is uncommon; hence, surgery is usually necessary. We present a case of a posttraumatic aneurysm in a child that occurred after a fall from a large height and that spontaneously thrombosed.     

Intra-arterial fibrinolysis in acute thrombosis of the basilar artery

INTRODUCTION: Ischemia in the territory of the basilar artery presents with a variable clinical picture of hemiparesia-tetraplegia, progressive deterioration of level of consciousness, irregular respiration and apnea leading to irreversible coma and death in between 75% and 86% of cases. The usual treatment is supportive. CLINICAL CASE: We present the case of a 49 year old woman with acute thrombosis of the basilar artery and a progressive course leading to coma. No bulbar lesions were seen on the CT scan done in the Emergency Department. Thrombosis of the basilar artery and permeable bilateral carotid systems were shown on arteriography. There were no contra-indications to fibrinolysis. Following local fibrinolytic treatment with urokinase the patient had full recovery from her neurological disorder and no sequelae. The basilar artery remained permeable six months later. CONCLUSIONS: Emergency treatment with cerebral intra-arterial fibrinolysis within the first six hours, in a case of neurological deficit progressing in the basilar artery territory, with persistence of brain-stem functions and no signs of decerebration (provided there are no contra-indications to fibrinolysis and the initial cerebral CT scan shows no bulbar lesions) may save the patient's life, with total or partial recovery of brain-stem function.     

Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery after experimental subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Gene transfer with recombinant viral vectors encoding vasodilator proteins may be useful in therapy of cerebral vasospasm after subarachnoid hemorrhage (SAH). Relaxations mediated by nitric oxide are impaired in cerebral arteries affected by SAH. The present study was designed to determine the effect of SAH on the efficiency of ex vivo adenovirus-mediated gene transfer to canine basilar arteries and to examine whether expression of recombinant endothelial nitric oxide synthase (eNOS) gene may have functional effects on vasomotor reactivity of spastic arteries affected by SAH. METHODS: Replication-deficient recombinant adenovirus vectors encoding bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVbeta-Gal) genes were used for ex vivo gene transfer. Rings of basilar arteries obtained from control dogs and dogs exposed to SAH were incubated with the vectors in minimum essential medium. Twenty-four hours after gene transfer, expression and function of the recombinant genes were evaluated by (1) histochemical or immunohistochemical staining, (2) beta-galactosidase protein measurement, and (3) isometric tension recording. RESULTS: Transduction with AdCMVbeta-Gal and AdCMVeNOS resulted in the expression of recombinant beta-galactosidase and eNOS proteins mostly in the vascular adventitia. The expression of beta-galactosidase protein was approximately 2-fold higher in SAH arteries than in normal arteries. Endothelium-dependent relaxations caused by bradykinin and substance P were suppressed in SAH arteries. The relaxations to bradykinin were significantly augmented in both normal and SAH arteries after AdCMVeNOS transduction but not after AdCMVbeta-Gal transduction. The relaxations to substance P were augmented by AdCMVeNOS transduction only in normal arteries. Bradykinin and substance P caused relaxations even in endothelium-denuded arteries, when the vessels were transduced with AdCMVeNOS. These endothelium-independent (adventitia-dependent) relaxations to bradykinin observed after AdCMVeNOS transduction were similar between normal and SAH arteries, whereas those to substance P were significantly reduced in SAH arteries compared with normal arteries. CONCLUSIONS: These results suggest that expression of recombinant proteins after adenovirus-mediated gene transfer may be enhanced in cerebral arteries affected by SAH and that successful eNOS gene transfer to spastic arteries can at least partly restore the impaired nitric oxide-mediated relaxations through local (adventitial) production of nitric oxide.     

Inhibitory actions of various vasorelaxants on the myogenic contraction induced by quick stretch studied in canine cerebral artery

Quick stretch at a rate of 10 cm/s with the amount of 30% of the initial muscle length (= 100%) produced a myogenic contraction in canine cerebral artery. The inhibitory actions of various vasorelaxants on the stretch-induced contraction were investigated. Ca2+ channel blockers (nicardipine, D-cis-diltiazem) inhibited the stretch-induced contraction by 50-60% at the concentrations which abolished high KCl-induced contraction. Inhibitions of the stretch-induced contraction by nitro-compounds (nitroglycerin, sodium nitroprusside) were about 50%. In contrast, inhibitions by the compounds which activate ATP-sensitive K+ channels (cromakalim, nicorandil, pinacidil) of the myogenic contraction in response to quick stretch were only 20%. Papaverine totally abolished the stretch-induced contraction. It is likely that all the vasorelaxant compounds tested in the present study except papaverine are beneficial in the sense that they do not suppress the intrinsic myogenic contraction, which may be related to the autoregulation of local blood flow.     

Distribution of coronary arterial capacitance in a canine model

The capacitative properties of the major left coronary arteries, left main (LM), left anterior descending (LAD), and left circumflex (LCX), were studied in 19 open-chest isolated dog hearts. Capacitance was determined by using ramp perfusion and a left ventricular-to-coronary shunt diastolic decay method; both methods gave similar results, indicating a minimal systolic capacitative component. Increased pericardial pressure (PCP), 25 mmHg, was used to experimentally alter transmural wall pressure. The response to increased PCP was different in the LAD vs. LCX; increasing PCP decreased capacitance in the LCX but increased capacitance in the LAD. This may have been due to the different intramural vs. epicardial volume distribution of these vessels and a decrease in intramural tension during increased PCP. Increased PCP decreased LCX capacitance by approximately 13%, but no changes in conductance or zero flow pressure intercept occurred in any of the three vessels, i. e., evidence against the waterfall theory of vascular collapse at these levels of PCP. Coronary arterial capacitance was also linearly related to perfusion pressure.     

Protein synthesis and immunoreactivities of contraction-related proteins in smooth muscle cells of canine basilar artery after experimental subarachnoid hemorrhage

We examined time-dependent changes in protein synthesis and in the immunoreactivities of representative contraction-related structural proteins in smooth muscle cells of canine basilar arteries after experimental subarachnoid hemorrhage (SAH). Protein synthesis was assessed by the percentage of polyribosome-forming ribosomes to total ribosomes (aggregation rate), a morphological index of the activity of protein synthesis. The aggregation rates in prostaglandin F2 alpha-(PGF 2 alpha) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced contracted basilar arteries were 70.0 +/- 7.0% and 71.4 +/- 8.7%, respectively, quite similar to the value in normal basilar artery (73.0 +/- 8.0%). In the single-SAH group with little delayed histological changes in the basilar arteries, the aggregation rate was significantly decreased to 30.5 +/- 6.4% by 24 h after the SAH, and recovered to 52.3 +/- 9.0% and 70.2 +/- 7.6% at 7 and 14 days postSAH, respectively, when the vasospasm was moderately and completely ameliorated. In contrast, in the double-SAH group in which the basilar arteries developed delayed smooth muscle cell death and long-lasting arterial contraction, a significant decrease in the aggregation rate (25.0 +/- 5.0% on day 4) persisted for 14 days. The in vitro incorporation of [3H]-leucine in the basilar arterial cells was also significantly suppressed 4 and 7 days after the initial SAH (1.2 +/- 0.4 and 1.4 +/- 0.3 x 10(3) dpm/mg protein) in the double-SAH group, as opposed to no significant decrease in the basilar artery at 7 days postSAH in the single-SAH group (1.9 +/- 0.6 x 10(3) dpm/mg protein). The immunoreactivity of alpha-smooth muscle actin, a contractile protein, demonstrated by immunohistochemistry and immunoblots, was not altered for up to 14 days even in the double-SAH group, but that of calponin and of h-caldesmon, contraction-inhibiting proteins, was markedly reduced 4-14 days after the initial SAH. Persistent impairment of protein synthesis and relative reduction of immunoreactivities of the contraction-inhibiting proteins were observed in arteries with severe vasospasm and loss of smooth muscle cells, as noted in the double-SAH subjects. These abnormalities may cooperate to cause cerebral arterial narrowing accompanied by degeneration of smooth muscle cells after SAH.     

Impairment of bacterial clearance induced by norepinephrine infusion in rabbits

OBJECTIVE: Purpose of the study was to investigate the potential influence of norepinephrine (NE) on immune functions in terms of systemic and organ-specific bacterial clearance in rabbits. DESIGN: To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) CFU) were injected intravenously 60 min after starting the NE infusion at a low dose (1 microgram/kg per min, n = 6), causing an increase (30 mmHg) in mean arterial pressure without affecting the oxygen uptake, and at a higher dose (7.5 micrograms/kg per min, n = 6), resulting in a marked decrease (20%) in oxygen uptake, after infusion of NaCl solution (control, n = 6). In additional experiments (n = 6) NE (1 microgram/kg per min) was tested in endotoxemia induced by simultaneous infusion of endotoxin (40 micrograms/kg per h). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. RESULTS: NE infusion resulted in a dose-dependent prolonged elimination of the injected E. coli from the blood and in significantly higher (p < 0.05) numbers of CFU in liver and lung compared to the controls. Significant impairment of bacterial clearance was found after shock-producing endotoxemia, whereas simultaneous infusion of NE and endotoxin caused only a slightly delayed blood clearance of the injected bacteria. CONCLUSION: NE dose dependently affected bacterial clearance, which might be due to ischemia-derived hypoxic impairment of the phagocytosis and lysis function of the reticuloendothelial system, whereas NE improved elimination of bacteria in a state of endotoxic shock.     

Impairment of endothelial function induced by glyc-oxidized lipoprotein a [Lp(a)]

Diabetic patients develop endothelial dysfunction early in the course of the disease. Atherogenic lipoproteins such as LDL and Lp(a) are important risk factors for endothelial dysfunction and undergo nonenzymatic glycation in hyperglycaemia. Here we assessed whether glycation of Lp(a) potentiates its damaging influence on endothelial function. Human Lp(a) was glycated by dialyzation for 7 days against buffer containing 200 mmol/l glucose, or sham-treated without glucose and oxidized by incubation with Cu++. The degree of glycation accounted to 32 +/- 4%, and glycation rendered Lp(a) more susceptible to oxidative modification when exposed to Cu++. Isolated rings of rabbit aorta were superfused with physiological salt solution, and isometric tension was recorded. Incubation of the aortic rings with sham-treated or with 30 microg/ml glycated Lp(a), not oxidized, had no influence on acetylcholine-induced, endothelium-dependent relaxation. Exposure of the aortic rings to 30 microg/ml oxidized non-glycated (ox) Lp(a) caused a significant inhibition (19% at 1 microM acetylcholine) of the endothelium-dependent relaxation. Incubation of aortic rings with 30 microg/ml oxidized glycated (glyc-ox) Lp(a) attenuated endothelium-dependent relaxation more potently than oxLp(a) (by 34% at 1 microM acetylcholine). The presence of diethyl-dithio-carbamate (DDC), an inhibitor of the endogenous superoxide dismutase (SOD), potentiated the inhibition of relaxation induced by oxLp(a) and by glyc-oxLp(a) [38% inhibition at 1 microM acetylcholine for oxLp(a), and 49% inhibition at 1 microM acetylcholine for glyc-oxLp(a)]. Co-incubation with the O2- scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid disodium salt (TIRON) prevented the inhibition of relaxation by the oxidized lipoproteins, suggesting that enhanced NO-inactivation by O2- could be the underlying mechanism for the impairment of endothelium-dependent dilations by ox- and glyc-oxLp(a). The concentration of lysophosphatidycholine, a lipoprotein oxidation product and stimulus for O2- formation, was significantly enhanced in oxLp(a) and in glyc-oxLp(a) compared to native lipoproteins. Conclusion: Glycation enhances the endothelium-damaging influence of oxLp(a), presumably by enhancing oxidative stress. The likely mechanism for attenuation of endothelium-dependent dilations is increased formation of O2-, resulting in inactivation of nitric oxide. This mechanism may play an important role in diabetic patients and may contribute to disturbed organ perfusion.     

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

Glomerular mesangial cells are regarded as specialized smooth muscle cells located within the renal glomeruli and fulfilling important functions in glomerular physiology and pathophysiology. Here, we report that activation of the cyclic AMP signalling pathway by dibutyryl cyclic AMP, forskolin, or the beta 2-adrenergic receptor agonist salbutamol results in induction of apoptosis in mesangial cells. Activation of the apoptotic programme results in DNA fragmentation which is visible for most forms of apoptosis and is paralleled by enrichment of cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH-fragmented DNA ends and typical nuclear chromatin condensation. Induction of apoptosis was found to be dependent on translation and independent of nitric oxide synthase activity.     

Pterional craniotomy via a transcavernous approach for the treatment of low-lying distal basilar artery aneurysms

OBJECT: The author describes a surgical procedure in which pterional craniotomy is performed via a transcavernous approach to treat low-lying distal basilar artery (BA) aneurysm. This intradural procedure is compared with the extradural procedure described by Dolene, et al. METHODS: The addition of a transcavernous exposure to the standard pterional intradural transsylvian approach allows a lower exposure of the distal BA behind the dorsum sellae. The technical steps involved in this procedure are as follows: 1) removal of the anterior clinoid process: 2) entry into the cavernous sinus medial to the third nerve; 3) packing of the venous channels of the cavernous sinus lying between the carotid artery and the pituitary gland to open this space; 4) removal of the posterior clinoid process and the portion of the dorsum sellae that is exposed from within the cavernous sinus; and 5) removal of the exposed dura mater to obtain additional exposure of the peri-mesencephalic cistern. Eight cases of aneurysms of the distal BA are presented to illustrate how this approach can help in their surgical treatment. CONCLUSIONS: Using the standard pterional approach, these distal BA aneurysms were found to be either too low relative to the posterior clinoid process for adequate exposure or there was insufficient room for temporary clipping of the BA proximal to the lesion. The addition of a transcavernous exposure eliminated these technical problems and aneurysm clipping could be accomplished in each case.     

Characterization of a membrane calcium pathway induced by rotavirus infection in cultured cells

Some viruses induce changes in membrane permeability during infection. We have shown previously that the porcine strain of rotavirus, OSU, induced an increase in the permeability to Na+, K+, and Ca2+ during replication in MA104 cells. In this work, we have characterized the divalent cation entry pathway by measuring intracellular Ca2+ in fura-2-loaded MA104 and HT29 cells in suspension. The permeability to Ca2+ and other cations was evaluated by the change of the intracellular concentration following an extracellular cation pulse. Rotavirus infection induced an increase in permeability to Ca2+, Ba2+, Sr2+, Mn2+, and Co2+. The rate of cation entry decreased over time as the intracellular concentration increased during the first 20 s. This indicates that regulatory mechanisms, including channel inactivation, are triggered. La3+ did not enter the cell and blocked the entry of the divalent cations in a dose-dependent manner. Metoxyverapamil (D600), a blocker of L-type voltage-gated channels, partially inhibited the entry of Ca2+ in virus-infected MA104 and HT29 cells. The results suggest that rotavirus infection of cultured cells activates a cation channel rather than nonspecific permeation through the plasma membrane. This activation involves the synthesis of viral proteins through mechanisms yet unknown. The increase in intracellular Ca2+ induced by the activation of this channel may be related to the increase in cytoplasmic and endoplasmic reticulum Ca2+ pools required for virus maturation and cell death.     

Acute arterial hypertension caused by dissecting aneurysm of the renal artery

BACKGROUND: Aneurysm of the renal artery is an uncommon discovery at arteriography performed as part of a hypertension work-up. CASE REPORTS: We observed acute hypertension following dissection of a renal artery aneurysm which led to circulating channel stenosis. After surgical correction of the lesion, arterial pressures returned to normal. DISCUSSION: Most cases of renal artery aneurysm do not cause hypertension. In such cases, the high blood pressure is idiopathic or related to fibrodysplastic stenosis of the renal artery often associated with aneurysm formation. In rare cases with obstructive complications alone an aneurysm may lead to acute hypertension either after dissection as in our case or after thrombus formation. Surgery is generally required.     

Inhibition of arterial thrombosis by recombinant annexin V in a rabbit carotid artery injury model

BACKGROUND: The procoagulant effect of anionic phospholipid may play a major role in the development of arterial thrombosis. METHODS AND RESULTS: Annexin V, a calcium-dependent anionic-phospholipid-binding protein, was expressed and isolated from Escherichia coli and its antithrombotic effect examined in a rabbit carotid artery thrombosis model. A partially occlusive thrombus was formed in the left carotid artery by application of electric current to produce an approximately 50% occlusion of the lumen. After the current was discontinued, flow ceased completely within 42+/-12 minutes (n=6) because of continuing platelet/fibrin thrombus formation. When annexin V was given at doses of 2.8 to 16.6 microg x kg(-1) x min(-1) for a period of 180 minutes, starting at the time the current was stopped, there was a dose-dependent inhibition of thrombus formation. At a dose of 5.6 microg x kg(-1) x min(-1), blood flow remained patent throughout the infusion and for an additional 60 minutes after the infusion was stopped. In addition, there was a decrease in thrombus weight (16+/-7.4 versus 2.0+/-1.0 g), (125)I-fibrin deposition (approximately 45% reduction, P<.001), and (111)In-labeled platelet accumulation (approximately 43% reduction, P<.001). Prior mixing of annexin V with phosphatidylserine micelles abolished the antithrombotic effect of annexin V, whereas mixing with phosphatidylcholine micelles had no effect. The antithrombotic effect of annexin V was not associated with bleeding tendency, as judged by the amount of blood absorbed in a gauze pad placed in a surgical incision extending to the muscle tissue and by the standard template bleeding time. CONCLUSIONS: These observations support a potentially important role for anionic phospholipid exposure in platelets in arterial thrombosis, and inhibition of this activity could be a novel target for therapy in coronary thrombosis and stroke and after angioplasty.     

A histomorphological study in age related changes in the elastic fiber system of the basilar artery

The aim of the study was to quantify the distribution of elastic fibers within the wall of the basilar artery. Three age groups were studied: 1) 0-1 yr.; 2) 20-50 yr. 3) > 50 yr. A histomorphometrical study was undertaken using an estimation of the linear density of the components of the fibrous elastic tissue system: the full length in the proximal and distal segments of the basilar artery was evaluated. Our results showed that: The elastic tissue of the basilar artery is not evenly distributed throughout the tunica media. Compared to the 0 to 1-year age group, mature elastic, elauninic and oxytalan fibers decreased with age. In all age groups the linear density of the mature elastic fibers was more evident in the proximal than in the distal segment of the artery.     

A comparative assessment of cerebral haemodynamics in the basilar artery and carotid territory by transcranial Doppler sonography in normal subjects

In 69 healthy volunteers (34 males, 35 females, age range 17-80 years) we compared the following haemodynamic parameters between the basilar artery and carotid artery system, assessed by transcranial Doppler sonography: mean blood velocity, pulsatility index and the hemispheric indices as ratios of the middle, anterior and posterior cerebral arteries with the internal carotid artery (MCA/ICA, ACA/ICA, PCA/ICA) and of the PCA with the basilar artery (PCA/BA), as well as the ACA/MCA and the MCA/BA ratio. In all arteries (ICA, MCA, ACA, PCA and BA) mean blood velocity decreased significantly with advancing age (p < 0.01) and was significantly higher in females as compared to males (p < 0.05). The pulsatility index increased significantly with age in the ICA, MCA, ACA and BA (p < 0.01) and showed no sex differences in any of the intracranial arteries except for the ACA. The MCA/ICA and ACA/ICA index declined significantly with advancing age (p < 0.005, p < 0.05, respectively) and with increasing heart rate (p < 0.01 for both arteries), while the ACA/MCA, the PCA/BA and the MCA/BA ratio remained unchanged by age and heart rate. We conclude that there is no striking difference in the cerebral haemodynamics of the basilar artery and the carotid artery supplied territories.     

Mechanism of endothelium-dependent relaxation induced by thrombin in the pig coronary artery

The present study describes the characterization of the binding properties and autoradiographic distribution of a new nonpeptide antagonist of neurotensin receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3-carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain. The binding of [3H]SR 142948A in brain membrane homogenates was specific, time-dependent, reversible and saturable. [3H]SR 142948A bound to an apparently homogeneous population of sites, with a Kd of 3.5 nM and a Bmax value of 508 fmol/mg of protein, which was 80% higher than that observed in saturation experiments with [3H]neurotensin. [3H]SR 142948A binding was inhibited by SR 142948A, the related nonpeptide receptor antagonist, SR 48692 (2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole -3-carbonyl]amino]-adamantane-2-carboxylic acid) and neurotensin. Saturation and competition studies in the presence or absence of the histamine H1 receptor antagonist, levocabastine, revealed that [3H]SR 142948A bound with similar affinities to both the levocabastine-insensitive neurotensin NT1 receptors (20% of the total binding population) and the recently cloned levocabastine-sensitive neurotensin NT2 receptors (80% of the receptors) (Kd = 6.8 and 4.8 nM, respectively). The regional distribution of [3H]SR 142948A binding in the rat brain closely matched the distribution of [125I]neurotensin binding. In conclusion, these findings indicate that [3H]SR 142948A is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and NT2 receptors and represents thus an excellent tool to study neurotensin receptors in the rat brain.     

Role of basic fibroblast growth factor in the regulation of rat basilar artery tone in vivo

An antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 blocks the analgesic actions of the mu 1 analgesics morphine and [D-Ala2,D-Leu5]enkephalin (DADL) when they are microinjected into the periaqueductal gray. In contrast, morphine-6 beta-glucuronide (M6G) analgesia is unaffected by this treatment. Antisense oligodeoxynucleotides directed against distinct Gi alpha subunits also distinguish between morphine and M6G analgesia. A probe targeting Gi alpha 2 blocks morphine analgesia, as previously reported, but is inactive against M6G analgesia. Conversely, an antisense oligodeoxynucleotide against Gi alpha 1 inhibits M6G analgesia without affecting morphine analgesia. The antisense oligodeoxynucleotide directed against G(o)alpha is ineffective against both compounds. These results confirm the prior association of Gi alpha 2 with morphine analgesia and strongly suggests that M6G acts through a different opioid receptor, as revealed by its insensitivity towards the MOR-1 antisense probe and differential sensitivity towards G-protein alpha subunit antisense oligodeoxynucleotides.