Beta-adrenoceptor and epoprostenol (prostacyclin) responsiveness of lymphocytes in migraine patients

Abstract

SummaryBeta-adrenoceptor blocking drugs are of prophylactic value in some patients with migraine. Beta-adrenoceptor responsiveness as measured by lymphocyte cAMP responsiveness to isoprenaline has, therefore, been compared in ten untreated classical migraine patients and ten matched non-migraine control subjects. Lymphocyte responsiveness to epoprostenol (prostacyclin, PGI2) was also compared. No difference in response to either agent was found between the two groups. A generalized abnormality of betaadrenoceptor function does not appear to be present in classical migraine, but a defect localized to specific vascular regions cannot be excluded.KEY WORDS: isoprenaline, cyclic AMP. IntroductionThe relationship between cardiovascular, neurological and haematological factors in the pathogenesis of migraine is not understood nor, consequently, is the mode of action of prophylactic migraine treatments. As a preliminary study to examination of beta-adrenoceptor and PGI2 receptor functional status during prophylactic treatment of classical migraine with beta-blockers, we have examined the general responsiveness of these vasodilating receptor systems during attack free periods. Beta-adrenoceptor and PGI2 receptor responsiveness was examined on lymphocytes by measuring isoprenaline and PGI2

Differential Changes in Receptor‐Mediated Transduction in Migraine and Cluster Headache: Studies on Polymorphonuclear Leucocytes

“…4 However the response of PMNs from lithium treated cluster headache patients was significantly reduced to approximately half that of untreated acute cluster headache patients and controls. These results show a marked depression in responsiveness to CF in PMNs from migraine subjects decreasing to approximately half that found in control subjects.…”

“…In contrast, PMNs from untreated cluster headache subjects (acute or quiescent) show no depression in responsiveness unlike the reduced adenylate cyclase activity induced by prostacyclin from lymphocytes from cluster headache patients. 4 However the response of PMNs from lithium treated cluster headache patients was significantly reduced to approximately half that of untreated acute cluster headache patients and controls.…”

“…1,2,3 Receptor activated cyclic AMP production in lymphocytes of cluster headache patients shows a significant reduction in response in the absence of a change in receptor number or affinity, indicating a defect in coupling between the receptor and adenylate cyclase, a process which is highly dependent on multiple membrane components. 2 No such effect is seen in migraine patients, 4 although the possibility that membrane function is abnormal is indicated from the fact that a diverse range of prophylactic and acute drug treatments, eg, 5-hydroxytryptamine (5HT) antagonists and beta blockers, are used successfully in migraine. In fact drugs effective in migraine may exacerbate cluster headache, whereas, conversely, drugs widely used in treatment of cluster headache, eg lithium, exacerbate migraine, 5 indicating that distinct and possibly antagonist systems may be involved in their therapeutic actions.…”

A Review of Prostanoid Receptors: Expression, Characterization, Regulation, and Mechanism of Action

“…Ligand binding properties for hIP have been characterized in platelet membranes by displacement of [ 3 H]iloprost, an IP‐specific agonist (Jones et al 2009; Siegl et al 1979; Tsai et al 1989; Crider et al 2001) (Tables 2 and 6) instead of PGI 2 due to the short half‐life of the latter. Ligand efficacies for hIP have been determined in platelet membranes (Fitscha et al 1987; Stürzebecher and Losert 1987; Kobzar et al 2001), vascular smooth muscle (Angulo et al 2002; Hadházy et al 1986; Baxter et al 1995, lymphocytes (Kilfeather et al 1984), and recombinant human IP expressed in COS‐1 (Crider et al 2001) and MEG‐01 (Tunaru et al 2016) cells (Table 6). Although other PG receptors are present in the human tissue samples, the EC 50 values clearly indicate that any cross‐reactivity of PGI 2 with the other receptors would result in negligible response.…”

Expression of prostaglandin I2 (prostacyclin) receptor in blood of migraine patients: A potential biomarker

“…In studies that have been done so far about the receptor of PGI2 in migraine, the effect of inhibitors has been noticed. [ 13 14 ]…”